EUROPE Technologies EUROPE 27 - 30 November 2018 · Comprehensive sponsorship packages allow you to...

2018 PROGRAM27 NOVEMBER

Organ-on-a-Chip and MicroPhysiological Systems

Single-Cell Analysis

Artificial Intelligence & Machine Learning for Drug Discovery

28 - 29 NOVEMBER

Optimizing Leads and Predicting Drug Toxicity

Preclinical Models for Cancer Immunotherapy and Combinations

Target Identification & Validation Strategies

Nash and Fibrosis: Translational Research and Strategies

29 - 30 NOVEMBER

3D Cellular Models

Translational Biomarkers in Immuno-Oncology

CNS Models and Translational Strategies

Induced Pluripotent Stem Cells

27 - 30 November 2018Sheraton Lisboa Hotel & Spa • Lisbon, Portugal

Where Preclinical Minds Meet Discovery TechnologiesEUROPE

27-30 November 2018Sheraton Lisboa Hotel & SpaLisbon, Portugal

3rd Annual

EUROPE27-30 November 2018Sheraton Lisboa Hotel & SpaLisbon, Portugal

3rd Annual

CORPORATE SPONSORS

FINAL AGENDA

A Division of Cambridge Innovation Institute

FINAL WEEKS TO REGISTER!

Cover

Short Courses





NASH and Fibrosis: Translational Research and Strategies

3D Cellular Models






Sponsor & Exhibit Opportunities

Hotel & Travel Information

Registration Information

Register Online!WorldPreclinicalEurope.com

http://www.worldpreclinicaleurope.com/



Cover

Short Courses






3D Cellular Models










2017 Attendee Demographics

WorldPreclinicalEurope.com | 2

■ Biotech & Pharma 64%■ Academic & Government 27%■ Healthcare 5%■ Press & Services 4%

Company Type■ Europe 72%■ United States 14%■ Asia 12%■ Rest of World 2%

Geographic Location■ Scientist/Technologist 36%■ Executive & Director 26%■ Professor 12%■ Sales & Marketing 11%■ Manager 9%■ Assistant 6%

Delegate Title

Sponsor & Exhibit OpportunitiesComprehensive sponsorship packages allow you to achieve your objectives before, during, and long after the event. Signing on earlier will allow you to maximize exposure to hard-to-reach decision-makers.

Podium Presentations — Available within Main Agenda!Showcase your solutions to a guaranteed, targeted audience through a 15- or 30-minute presentation during a specific conference program, breakfast, lunch, or separate from the main agenda within a pre-conference workshop. Package includes exhibit space, on-site branding, and access to cooperative marketing efforts by CHI. For the luncheon option, lunches are delivered to attendees who are already seated in the main session room. Presentations will sell out quickly, so sign on early to secure your talk!

One-on-One MeetingsSelect your top prospects from the pre-conference registration list. CHI will reach out to your prospects and arrange the meeting for you. A minimum number of meetings will be guaranteed, depending on your marketing objectives and needs. A very limited number of these packages will be sold.

Invitation-Only VIP Dinner/Hospitality SuiteSponsors will select their top prospects from the conference pre-registration list for an evening of networking at the hotel or at a choice local venue. CHI will extend invitations and deliver prospects, helping you to make the most out of this invaluable opportunity. Evening will be customized according to sponsor’s objectives. (i.e.: Purely social, Focus group, Reception style, Plated dinner with specific conversation focus)

EXHIBITExhibitors will enjoy facilitated networking opportunities with qualified delegates, making it the perfect platform to launch a new product, collect feedback, and generate new leads. Exhibit space sells out quickly, so reserve yours today.

Additional branding & promotional opportunities include:• Hotel Room Keys• Footprint Trails• Staircase Ads• Conference Tote Bags

• Literature Distribution (Tote Bag Insert or Chair Drop)

• Badge Lanyards• Padfolios• Program Guide Advertisement

Looking for additional ways to drive leads to your sales team?CHI’s Lead Generation Programs will help you obtain more targeted, quality leads throughout the year. We will mine our database of 800,000+ life science professionals to your specific needs. We guarantee a minimum of 100 leads per program! Opportunities include:• Live Webinars• White Papers

• Market Surveys• Podcasts and More

Companies A-KRod EymaelManager, Business Development [email protected]

Companies L-ZJoseph Vacca, M.S.Director, Business [email protected]

For more information, please contact:

EXHIBIT PRICING EXHIBIT FLOORPLAN


mailto:reymael%40healthtech.com?subject=

mailto:[email protected]

http://www.worldpreclinicaleurope.com/docs/librariesprovider11/2018/wpe-exhibit-contract.pdf

http://www.worldpreclinicaleurope.com/docs/librariesprovider11/2018/wpe_floor_plan.pdf



Cover

Short Courses






3D Cellular Models










Short Courses*

27 NOVEMBER 2018 | 18:00-20:30

SC1: Immunology Basics for Drug Discovery, Part 1: Immune System OverviewThis short course provides an introduction to human immunology for discovery pharmacologists, biologists and chemists working in the biopharmaceutical industry. It will review how the immune system is organized and gives rise to both normal and pathogenic immune responses. Topics will include pathogen recognition by innate immune cells, antigen generation and presentation to lymphocytes, effector mechanisms of T cells, antibody generation and the molecular basis of pathogenic immune responses.Instructor: Thomas Sundberg, PhD, Senior Research Scientist I, Center for Development of Therapeutics, Broad Institute of MIT and Harvard

SC2: Understanding Key Concepts in Drug Metabolism and Drug TransporThis short course will focus on basic aspects of drug metabolism and drug transporters and their impact in drug research and development. The drug metabolism section will briefly cover the historical basis of early drug metabolism studies, important biotransformations with relevant mechanistic details, some strategies that medicinal chemists use to influence drug metabolism and finally, the role of reactive metabolites in drug toxicity. The drug transporter section will cover conceptual aspects of experimental design, including set-up, pitfalls and data interpretation. The relevance of drug transport processes for key ADME and safety properties will be discussed and exemplified with different case studies. The audience will learn where and how drug transport properties can be optimized throughout lead-optimization to improve drug absorption and distribution, organ targeting and drug safety.Instructors:John C. L. Erve, PhD, DABT, Jerve Scientific Consulting, Inc.Bruno Stieger, PhD, Department of Clinical Pharmacology and Toxicology, University Hospital Zurich

SC3: The Origins, Optimization and Application of Organ-on-a-Chip SystemsThis short course will take a more in depth look at the origins, optimization and application of organ-on-a-chip systems. This course will cover the essential tools and techniques employed in the development and application of organ-on-a-chip and MicroPhysiological systems in more detail. Topics covered will include the integration of non-biological chips with modern cell culture, microfabrication techniques, 2D and 3D applications, increasing throughput and insuring quality control. Participants can expect to gain a greater understanding of the history and background of organ-on-a-chip devices, their current capabilities, current and future industrial applications.Instructors:James J. Hickman, PhD, Professor, NanoScience Technology Center, University of Central FloridaPeter Loskill, PhD, Assistant Professor for Experimental Regenerative Medicine, Department of Women’s Health, Research Institute for Women’s Health, Faculty of Medicine, Eberhard Karls University TübingenWendy Rowan, PhD, FRSB, Associate GSK Fellow, Scientific Leader Target Sciences, GlaxoSmithKline

29 NOVEMBER 2018 | 19:30-21:00

SC4: Immunology Basics for Drug Discovery, Part 2: Immune-Oncology and AutoimmunityThis short course will provide a brief overview of the organization of the immune system that will then serve as the basis for discussions of how the immune system can be modulated through biopharmaceutical intervention to either enhance anti-tumor immunity or suppress pathogenic inflammation. We will cover basic principles of immune-oncology (e.g., checkpoint blockade) and progress in targeting immune processes with small molecules and protein-based immunomodulatory therapies.Instructor: Thomas Sundberg, PhD, Senior Research Scientist I, Center for Development of Therapeutics, Broad Institute of MIT and Harvard

SC5: Humanized Mouse Models: Technology and Applications in Preclinical Assessment of Cancer ImmunotherapyHumanized mouse models have been developed as immunologically relevant models for preclinical profiling of cancer immunotherapies. The course will describe different types of humanized mouse models, their immune characterization, and specific examples of their application in the field of cancer immunotherapy. The course will highlight advantages and pitfalls of currently available humanized mouse models and will give an overview of the next-generation improved humanized models designed to better address specific immunological questions.Instructor: Michael Brehm, PhD, Associate Professor, The Robert and Sandra Glass Term Chair in Diabetes, Diabetes Center of Excellence, Program in Molecular Medicine, University of Massachusetts Medical School


*Separate registration is required.


Microfabrication techniques such as 3D printing have enabled the synthesis of highly specialised and controlled microchips with well-defined chemical and physical environments. The integration of such chips with modern cell culture techniques has created a new way to mimic the in vivo. Growing excitement around these microphysiological models of human organs on microfluidic cell culture chips has led to a marked interest and investment in such technologies, yet many challenges remain ahead, not least of all scalability and adaptation for high throughput screening. Join us for Cambridge Healthtech Institute’s inaugural Organ-on-a-Chip and MicroPhysiological Systems symposium, where this promising preclinical model will be explored and evaluated, where future steps towards more accurate and reliable preclinical trials will be taken.

Recommended All Access Package:27 November: Organ-on-a-Chip and MicroPhysiological Systems27 November Dinner Course: SC3: The Origins, Optimization and Application of Organ-on-a-Chip Systems28-29 November: Optimizing Leads and Predicting Drug Toxicity29-30 November: 3D Cellular Models29 November Dinner Course: SC5: Humanized Mouse Models: Technology and Applications in Preclinical Assessment of Cancer Immunotherapy

TUESDAY 27 NOVEMBER

7:00 Registration and Morning Coffee

SINGLE SYSTEM MODELS8:20 Welcome RemarksJoel Hornby, BSc, Conference Director, Cambridge Healthtech Institute

8:25 Chairperson’s Opening RemarksJames J. Hickman PhD, Professor, NanoScience Technology Center, University of Central Florida

8:30 Stem Cell Based MicroPhysiological Organ-on-a-Chip Systems as in vitro Models of Human Tissue with Physiological Structure and FunctionPeter Loskill, PhD, Assistant Professor for Experimental Regenerative Medicine, Department of Women’s Health, Research Institute for Women’s Health, Faculty of Medicine, Eberhard Karls University TübingenDrug discovery and development to date has relied on animal models, which fail to resemble human physiology. The discovery of human induced pluripotent stem cells (hiPSC) has led to the emergence of a new paradigm of drug screening using patient- and disease-specific organ/tissue-models. One promising approach is the organ-on-a-chip system that integrates hiPSC-derived tissues in microphysiological environments and combines human genetic background, in vivo-like tissue structure, physiological functionality, and “vasculature-like” perfusion.

9:00 Lung Alveolar Models Based on Organs-on-Chip TechnologiesOlivier Guenat, PhD, Head Organs-on-Chip Technologies, ARTORG Center, University of BernOrgans-on-chips are able to recapitulate the in vivo cellular environment in unprecedented way and are widely expected to better predict drug’s response in humans than standard in vitro models. We will present several lung-on-chip models using primary cells from patients that closely recapitulate the cellular environment of the lung parenchyma. These functional models, which mimic the lung alveolar barrier as well as the lung microvasculature, are used to evaluate the effects of various compounds used for respiratory diseases, such as pulmonary fibrosis.

9:30 Development of Organ-on-a-Chip Systems for Disease Modeling In the Vasculature, Liver & GutMatthew Lech, ScM., Senior Scientist, Inflammation & Immunology Research Unit, PfizerThe current drug development process results in many clinical trial failures due, in part, to poor translation from early stage development with simple in vitro assays through in vivo preclinical models which do to properly replicate human disease. Companies can do little to recover the effort and cost associated with a clinical trial failure. We are developing three human organ-on-a-chip systems for improved drug development; the liver, vasculature and gut.

10:00 Coffee Break

MULTI SYSTEM MODELS10:30 Building Phenotypic Body-on-a-Chip Models for Preclinical Toxicological and Efficacy Evaluations Utilizing Stem Cell Derived Disease ModelsJames J. Hickman, PhD, Professor, NanoScience Technology Center, University of Central FloridaThe utilization of human-on-a-chip systems that incorporate iPSCs allows for understanding different disease states by constructing them utilizing patient cells. We are constructing systems in serum-free medium with functional readouts that employs a pumpless platform. Our group has been constructing these systems with up to 6 organs and demonstrated up to 28 days evaluation of drugs and compounds, that have shown similar response to results seen from clinical data or literature reports.

Inaugural

Organ-on-a-Chip and MicroPhysiological SystemsComplex Cellular Models in Physiologically Relevant Environments

SYMPOSIUM | 27 NOVEMBER 2018



Cover

Short Courses






3D Cellular Models













11:00 Emulating the Gut-Liver Axis - Organ-on-Chip in Preclinical ResearchAlexander S. Mosig, PhD, Assistant Professor, Center for Sepsis Control and Care, Jena University HospitalTo investigate the mechanism of infection-related organ dysfunction we developed a microfluidically perfused model of the human gut-liver axis. The in vitro model comprises tissue resident and circulating immune cells to emulate essential components of the human immune system. Biochip-integrated sensors allow continuous monitoring of environmental conditions and allow quantification of tissue integrity. A synthetic microbiome is being integrated to emulate microbiome-host interaction under physiological and pathophysiological conditions.

11:30 Enjoy Lunch on Your Own

TRANSLATIONAL AND APPLIED SYSTEMS13:25 Chairperson’s RemarksPeter Loskill, PhD, Assistant Professor for Experimental Regenerative Medicine, Department of Women’s Health, Research Institute for Women’s Health, Faculty of Medicine, Eberhard Karls University Tübingen

13:30 Modeling Rare Diseases with Organs-on-ChipsDanilo A. Tagle, MS, PhD, Associate Director for Special Initiatives, National Center for Advancing Translational Sciences, National Institutes of HealthDeveloping drugs for rare diseases can be challenging due to the small, heterogeneous patient populations, few disease experts and expert centers, variable and long time-frames for disease progression, a poor understanding of disease natural history, and a lack of prior clinical studies. Recent technological advances, particularly in the area of organs-on-chips and induced pluripotent stem cells (iPSCs) have created opportunities to create a paradigm shift in therapy development, especially in the area of rare disease research.

14:00 Reducing Attrition in Drug Discovery through the Use of Human Translational Cellular ModelsWendy Rowan, PhD, FRSB, Associate GSK Fellow, Scientific Leader Target Sciences, GlaxoSmithKlinePreclinical efficacy and toxicology data derived from in vitro and animal models often fails to translate to clinical trials, resulting in high rates of attrition and falling Research and Development productivity. The development of more predictive human in vitro systems represents one of the most urgent challenges facing the pharmaceutical industry. In a fast moving field, advances in bioengineering are showing the potential for transforming the outcome of drug discovery.

14:30 Maximizing the Impact of MicroPhysiological Systems with in vitro-in vivo TranslationMurat Cirit, PhD, Director, Biological Engineering, MITMicrophysiological systems (MPS) hold promise for improving therapeutic drug approval rates by providing more physiological, human-based, in vitro assays for preclinical drug development activities compared to traditional in vitro and animal models. The full impact of MPS technologies will be realized only when robust approaches for in vitro-in vivo (MPS-to-human) translation are developed and utilized and explain how the burgeoning field of quantitative systems pharmacology (QSP) can fill that need.

15:00 Refreshment Break

15:30 Credibility/Validity of Complex in vitro Models: Crowdsourcing Strategies to Facilitate Acceptance and UseSofia Batista Leite, PhD, Scientific/Technical Project Officer, Chemical Safety and Alternative Methods, ECVAM, European Commission – Joint Research Centre (EC-JRC)Complex in vitro models aim to represent higher-level anatomical and physiological aspects of human biology. Combined with their fast developing technology, these models are very attractive to multiple research and regulatory areas. Further implementation could be achieved by establishing a standardized framework for their assessment. More than 500 people responded to an EURL-ECVAM survey sharing their opinion on if/how such framework should/could be established. The survey results will be presented.

16:00 A Human Heart-Liver Platform to Study Acute and Chronic Cardiotoxicity upon Hepatic BiotransformationAnne Riu, PhD, Project Manager, Research and Innovation, L’OréalRegulation of cosmetic testing has spurred efforts to develop new methods for systemic toxicity, however, in vitro assays are often lacking xenobiotic metabolism. A heart-liver system was developed to study metabolism-dependent cardiotoxicity combining functional cardiac and metabolically competent hepatic modules maintained under flow for 14 days. The system was characterized with a set of reference compounds and then evaluated with cosmetic ingredients.

16:30 GUT ON-A-CHIP: Intestinal barrier model for studying host microbe-immune responsesEvita van de Steeg, PhD, Senior Scientist, Human Biology & Microbiology, TNO Pharma LeidenThe majority of screening and predictive models do not reflect the physiology of the human intestinal tract properly, resulting in low translational value to the clinical situation. We were able to fix human intestinal tissue in a microfluidic chip and maintain its functionality under physiological conditions for 24h. The new 3D printed chip is easy to use and will provide us with a higher throughput system.

17:00 Close of Symposium

18:00 – 20:30 Recommended Dinner Short Course*SC3: The Origins, Optimization and Application of Organ-on-a-Chip Systems* Separate registration required, see page 3 for details.



Cover

Short Courses






3D Cellular Models














Inaugural

Single-Cell AnalysisDevising Better Therapies through the Study of Homologous Populations


Single cell omics are rapidly redefining how scientists view heterogeneous cell populations in oncology. With high-throughput single cell technologies being developed for imaging, mass spectrometry and sequencing applications, the impact on healthcare industries is growing momentum, though this potential requires much nurturing before single cell technologies can be integrated for use with biomarkers for diagnostics and therapeutics. At Cambridge Healthtech Institute’s inaugural Single-Cell Analysis symposium, receive updates on the latest single cell technologies to disrupt the market and compare and contrast their benefits to existing technologies.

Recommended All Access Package:27 November: Single-Cell Analysis27 November Dinner Course: SC3: The Origins, Optimization and Application of Organ-on-a-Chip Systems28-29 November: Preclinical Models for Cancer Immunotherapy and Combinations29-30 November: CNS Models and Translational Strategies29 November Dinner Course: SC4: Immunology Basics for Drug Discovery, Part 2: Immune-Oncology and Autoimmunity

TUESDAY 27 NOVEMBER


TRANSCRIPTOMICS BASED METHODS8:20 Welcome RemarksJoel Hornby, BSc, Conference Director, Cambridge Healthtech Institute

8:25 Chairperson’s Opening RemarksDimitry Ofengeim, PhD, Lab Head, Neuroimmunology, Neuroscience, Sanofi

8:30 Therapeutic Approaches to the Nervous System: One Cell at a TimeDimitry Ofengeim, PhD, Lab Head, Neuroimmunology, Neuroscience, SanofiSingle-cell RNA sequencing (scRNA-seq) is a sequencing platform that enables the analysis of transcriptomes from individual cells and is ideally suited to address the inherent complexity and dynamics of the central nervous system. There has been recent progress and challenges in applying scRNA-seq to advance our understanding of the brain in the application of this technology in the discovery of therapeutic targets and biomarkers for neurodegenerative diseases.

9:00 Single Cell Transcriptomic Analysis Workflow for Characterizing Complex Datasets of a Novel Human Corticogenesis ModelMarilisa Neri, PhD, Data Scientist, NIBR, NovartisSingle cell RNAseq is used to characterize a novel in vitro model of corticogenesis. Using our internally developed workflow, the neuronal differentiation has been characterized at cell granularity level: cell populations, marker genes and phenotype heterogeneity. Novel developed method for rare/sub cell types

identification, CellSIUS (Cell Subtype Identification from Upregulated gene Sets), enabled characterization of a novel protocol that recapitulates the full spectrum of cortical development, including upper-layer corticogenesis in vitro.

9:30 Spatial Transcriptomics - Bridging Histology and RNA SequencingMichaela Asp, PhD, Department of Gene Technology, Science for Life Laboratory, Royal Institute of TechnologySpatially resolved transcriptomics provides us with new insights into the molecular diversity of heterogeneous tissue structures. Several approaches have been established in order to preserve gene expression information together with its tissue localization. However, existing challenges for many spatial technologies include the extent of existing knowledge about the targets, the labor-intensive nature of the methods or the fact that they are not applicable to clinical samples. Here, we present a method whereby whole intact tissue sections can be studied in a spatial whole-transcriptome manner.

10:00 Coffee Break

MULTI-OMICS METHODS10:30 The Impact of Cell Proliferation and Microenvironment on Tumour HeterogeneityAnders Ståhlberg, PhD, Associate Professor, Clinical Pathology and Genetics & Sahlgrenska Cancer Center, University of Gothenburg & Sahlgrenska University HospitalHere, we will show how cell proliferation and cancer stem cell properties contribute to intratumor heterogeneity in two entities: breast cancer and liposarcoma. We will also describe how the microenvironment determines the cellular phenotype of individual cells. To outline cell fate mechanisms we employed various single-cell techniques and functional assays.

11:00 Subcellular Spatial Analysis of Transcriptome and Proteome during Early DevelopmentRadek Sindelka, PhD, Senior Scientist, Department of Gene Expression, Institute of Biotechnology, Czech Academy of Sciences, BIOCEVStarting from a single fertilized oocyte, through manifold of divisions a complex organism is developed that has distinct asymmetries. One of the main challenges in developmental biology is to understand how and when these asymmetries are generated and how they are controlled. The African clawed frog (Xenopus laevis) is an ideal model for studies of early development thanks to their very large oocytes. We have developed a unique platform based on RT-qPCR, RNA-Seq and UPLC-ESI-MS/MS to measure asymmetric localization of fate determining RNAs and proteins within the egg and among the early stage blastomeres.



Cover

Short Courses






3D Cellular Models













NOVEL SINGLE CELL METHODS13:25 Chairperson’s RemarksDimitry Ofengeim, PhD, Lab Head, Neuroimmunology, Neuroscience, Sanofi

13:30 The Future of Pre-Implantation Genetic Testing - Accurate and Non-InvasiveXiaoliang Sunney Xie, PhD, Lee Shau-kee Professor and Director of the Beijing Innovation Center for Genomics at Peking University, and Harvard University Visiting Professor, Biodynamic Optical Imaging Center, Peking UniversitySingle-cell whole-genome amplification is critical for IVF. Current whole-genome amplification (WGA) methods present low accuracy of copy-number variation (CNV) and low amplification fidelity. We developed MALBAC and LIANTI, achieving the highest precision for single-cell genome sequencing with quasi linear and linear amplification, respectively, as opposed to exponential amplification in PCR. Based on these, we developed MARSALA, NICS and MaReCs, to successfully select fertilized eggs free of chromosome abnormalities and devastating point mutations in more than 300 couples.

14:00 Metabolic Imaging of Single Cells Using Mass SpectrometryIan Gilmore, Senior NPL Fellow, National Centre of Excellence in Mass Spectrometry Imaging (NiCE-MSI), National Physical Laboratory (NPL)

14:30 Single Cell Mass Spectrometry in the Context of Drug DiscoveryCarla Newman, Investigator, Ex vivo Bioimaging, GlaxoSmithKlineA paradigm shift in the drug discovery workflow is required to reduce attrition and transform conventional drug screening assays into translatable analytical techniques for the analysis of drugs in complex environments, both in vitro and ex vivo. We propose the use of two mass spectrometry techniques: SIMS and static electrospray mass spectrometry to visualise unlabelled compounds inside the cell at physiological dosages that can offer valuable insight into the compound behaviour both on and off-target.


15:30 Single Cell AntibiogramsPiotr Garstecki, PhD, Professor, Microfluidics and Complex Fluids, Institute of Physical Chemistry, Polish Academy of SciencesDroplet microfluidics is an ideally suited technology for digital assays for bacterial cell counting and offers the possibility to probe the response of bacteria to antibiotics at the single cell level. The technology offers several interesting features – including alleviation of the unwanted inoculum effect in antibiogram assays and information on the distribution of susceptibility in the population.

16:00 Decoding Neuronal Diversity by Single Cell Convert-SeqJoachim Luginbuehl, PhD, JSPS Fellow, RIKEN YokohamaWe present Convert-seq, combining single-cell RNA sequencing (scRNA-seq) and pooled (mutiplexed) ectopic gene expression with a new strategy to discriminate sequencing reads derived from exogenous and endogenous transcripts. We demonstrate Convert-seq by associating hundreds of single cells at multiple time-points during direct conversion of human fibroblasts to induced neurons (iN) with exogenous and endogenous transcriptional signatures. Convert-seq is a broadly applicable workflow to rapidly identify key transcription factors orchestrating the direct conversion of virtually any cell type.

16:30 Droplet Microfluidics for High Throughput Biopharmaceuticals ScreeningHåkan Jönsson, PhD, Assistant Professor, KTH Royal Institute of TechnologyBiopharmaceuticals make up the majority of highest grossing drugs. Many protein therapeutics are produced in mammalian cell factories such as CHO or HEK293. Droplet microfluidics allows for single cell level high-throughput analysis of protein secretion. We present a platform based on split-GFP complementation in droplets, which enables screening of a heterogeneous variant library, transfectant pool enrichment by protein secretion and selection of a highly productive clone.


18:00 – 20:30 Recommended Dinner Short Course*SC3: The Origins, Optimization and Application of Organ-on-a-Chip Systems* Separate registration required, see page 3 for details.



Cover

Short Courses






3D Cellular Models










Hotel & Travel InformationConference Venue and Hotel: Sheraton Lisboa Hotel & SpaRua Latino Coelho, 11069-025 Lisbon, Portugal Phone: (351)(21) 3120000

Discounted Room Rate: €160 single/€180 double, includes breakfastDiscounted Room Rate Cut-off Date: 20 October 2018

Go to the travel page of www.WorldPreclinicalEurope.com for additional info






Inaugural

Artificial Intelligence & Machine Learning for Drug DiscoveryApplications in Target Discovery, Lead Optimization and Drug Safety


Artificial Intelligence (AI) and Machine Learning (ML) are more than just buzzwords being used in the pharmaceutical and biotechnology industry. There is now a steady stream of publications and evidence outlining what these terms really mean, how they can be applied in a drug discovery and development setting, and how much value they add in terms of saving time, effort and costs. Cambridge Healthtech Institute’s symposium on AI and Machine Learning for Drug Discovery will bring together computational and bioinformatics experts along with discovery scientists to discuss how some of these technologies and platforms are being used and how well they are living up to their promise. It will include a diverse set of talks that will highlight how AI and ML can be used for target identification, drug design and optimization, predicting drug toxicity and adverse events. This unique one-day symposium will help attendees meet and interact with experts and peers from around the world to share ideas and gain some understanding about the opportunities and limitations in using these emerging informatics tools and platforms.

Recommended All Access Package:27 November: Artificial Intelligence and Machine Learning for Drug Discovery27 November Dinner Course: SC2: Understanding Key Concepts in Drug Metabolism and Drug Transport28-29 November: Target Identification and Validation Strategies29-30 November: CNS Models and Translational Strategies29 November Dinner Course: SC5: Humanized Mouse Models: Technology and Applications in Preclinical Assessment of Cancer Immunotherapy

TUESDAY 27 NOVEMBER


USING MACHINE LEARNING TO ANALYZE AND PREDICT ADVERSE EVENTS AND DRUG TOXICITY

8:20 Welcome RemarksTanuja Koppal, PhD, Conference Director, Cambridge Healthtech Institute

8:25 Chairperson’s Opening RemarksMaria A. Miteva, PhD, Research Director, Molécules Thérapeutiques in silico (MTi), Inserm Institute

8:30 Introduction to Artificial Intelligence and Machine LearningArvind Rao, PhD, Associate Professor, Department of Computational Medicine and Bioinformatics, University of MichiganIn this introductory talk, we aim to familiarize the audience with basic ideas in machine learning for drug discovery, visiting concepts like dimension reduction, unsupervised and supervised learning using case-studies form drug-target prediction. The emphasis will be on developing and intuitive understanding of approaches and not on mathematical rigor.

9:00 Overview of How in silico Models Are Being Used to Predict Drug ToxicityAlexander Amberg, PhD, Computational Toxicologist, R&D Preclinical Safety, SanofiIn silico models are used for many different endpoints and in all phases of the drug development process, applied for the safety assessments of drug candidates and targets in the early research until later development phases, for registration as well as for marketed products. For this many different modelling approaches are used, like statistical structural fragment/fingerprint-based models, molecular descriptor-based QSAR models, systems toxicology models, simulation models up to newer machine learning models.

9:30 Integrated Mechanistic and Machine Learning Approach for Drug-Drug InteractionsMaria A. Miteva, PhD, Research Director, Molécules Thérapeutiques in silico (MTi), Inserm InstitutePredicting drug-drug interactions related to inhibition of drug metabolizing enzymes is key for drug toxicity. We will present in silico protocols integrating mechanistic and machine learning approaches to predict the inhibition of metabolizing enzymes by drug-like molecules and natural compounds. We will focus on cytochrome P450 (CYP), a supergene family of drug metabolizing enzymes responsible for the metabolism of approximately 90% of human drugs and the conjugate drug metabolizing enzymes sulfotransferases.

10:00 Coffee Break

10:30 Use of a Quantitative Systems Pharmacology (QSP) Model to Predict Liver Toxicity in Simulated PopulationsChristina Battista, PhD, Postdoctoral Fellow, University of North Carolina Institute for Drug Safety SciencesDILIsym®, the result of an ongoing public-private partnership, has been developed to investigate drug-induced liver injury (DILI). The model employs mathematical representations of mechanistic interactions following drug administration through the release of serum biomarkers to accurately predict clinical observations in simulated patient populations. This talk will outline DILIsym and discuss applications to date.



Cover

Short Courses






3D Cellular Models













11:00 KEYNOTE PRESENTATION: Observational Data for Biomedical DiscoveryNicholas P. Tatonetti, PhD, Herbert Irving Assistant Professor of Biomedical Informatics and Director of Clinical Informatics, Herbert Irving Comprehensive Cancer Center, Columbia UniversityData is transforming the scientific method across many domains. In drug safety, data from electronic health records and search logs are now being collected alongside traditional sources. These data sources present new opportunities for studying the phenomenological and molecular effects of active small molecules. However, they also present new challenges in data integration, statistical analysis, and nature of hypothesis generation. I will discuss these opportunities, challenges and their role in the future of drug safety science.

Sponsored by11:30 Present and Future Collaborative Drug Discovery Informatics InnovationsMariana Vaschetto, PhD, Head, Operations, EMEA, Collaborative Drug DiscoveryWe will present BioAssay Express (BAE) technology, the latest development from CDD. BAE streamlines the conversion of human-readable assay descriptions to computer-readable protocols. We will show how BAE is incorporated in CDD Vault, a secure hosted platform for storing, mining and sharing chemistry and biology data across multiple organizations.


AI-DRIVEN APPLICATIONS FOR DRUG DESIGN AND LEAD OPTIMIZATION

13:25 Chairperson’s RemarksNicholas P. Tatonetti, PhD, Herbert Irving Assistant Professor of Biomedical Informatics and Director of Clinical Informatics, Herbert Irving Comprehensive Cancer Center, Columbia University

13:30 Drug Discovery at the Speed of SoundShabnam Shaabani, PhD, Post-Doctoral Fellow, Drug Design Group, University of Groningen, The NetherlandsWe have introduced a novel approach towards preclinical drug discovery by blending Instant Chemistry, nL dispensing, acoustic-MS, uHTS and artificial intelligence. A prototype instrumentation platform is developed which allows for the parallel synthesis of hundreds of libraries of scaffolds on an unprecedented dense format. The platform is integrated with acoustic-MS and UPLC-MS for quality control and with different biophysical and phenotypical screening platforms. Artificial intelligence is developed to ensure never-seen-before fast cycle times for hit-to-lead progression optimizing against multiple parameters at the same time.

14:00 Network-Driven Drug Discovery (NDD) Approach in the Identification and Optimization of Small MoleculesSree Vadlamudi, PhD, Programme Manager, e Therapeutics plcWe have successfully implemented and validated a highly productive Network-driven Drug Discovery (NDD) platform comprises a suite of powerful, custom computational tools that tap into large-scale proprietary databases, and employs

data mining, machine learning, artificial intelligence, and network science to tackle complex diseases in an efficient and effective way. We will describe a case study highlighting the application of our proprietary NDD methodology in the discovery and optimisation of small molecules with a novel mechanism of action (MOA).

14:30 PANEL DISCUSSION: Understanding the Limitations and Caveats of Using Artificial Intelligence and Machine Learning ToolsThis discussion will bring together representatives from pharma, academia and technology companies to discuss the use as well as possible misuse of computational tools and big data for early drug development. The panel will also talk about how to identify and hopefully avoid ethical misuse of AI for clinical use and patient records.Moderator: Nicholas P. Tatonetti, PhD, Herbert Irving Assistant Professor of Biomedical Informatics and Director of Clinical Informatics, Herbert Irving Comprehensive Cancer Center, Columbia University


15:30 Computational Drug Repurposing Combining Image-Based Screens and Drug-Target DatabasesArvind Rao, PhD, Associate Professor, Department of Computational Medicine and Bioinformatics, University of MichiganWith drug-repurposing being a critical enterprise in mainstream clinical oncology, there is a need for infrastructure to integrate multiple modalities of data to prioritize drug candidates rationally. In this vein, we examine a scenario using machine learning methods to prioritize genetic modulators selected based on phenotypic (image-based) screening via RNAi. These screen-derived “hits” are then coupled with known drug-target interactions to repurpose candidate drugs for potential activity in breast cancer cells.

16:00 Computer-Aided Detection and Measurement of Subcutaneous Tumours in MiceJamshid Dehmeshki, PhD, Professor of Medical Image Computing and Image Analysis, Department of Computer Science, Kingston UniversityThis talk will explore how machine learning can aid diagnosis and drug development in cancer research. It will focus on how a novel new 3D measurement solution and machine learning are being used to measure and analyse subcutaneous mice tumours in major laboratories in the EU and USA to bring about improvements in scientific accuracy and animal welfare while offering the potential to decrease cost and duration of drug development.


18:00 – 20:30 Recommended Dinner Short Course*SC2: Understanding Key Concepts in Drug Metabolism and Drug Transport* Separate registration required, see page 3 for details.



Cover

Short Courses






3D Cellular Models














3rd Annual

Optimizing Leads and Predicting Drug ToxicityNew Tools. Better Predictions. Safer Drugs.

28-29 NOVEMBER 2018

There have been rapid changes in technology and approaches being utilized to bring safer and more effective drugs to the clinic. Despite those efforts, adverse drug events such as cardiotoxicity, hepatotoxicity and other organ toxicities, keep surfacing in the clinic, and idiosyncratic drug toxicity continues to haunt the drug development process. What can scientists do to ensure that the lead compounds are optimized and validated early and accurately to avoid costly mistakes from happening later in drug development? Cambridge Healthtech Institute’s conference on Optimizing Leads and Predicting Drug Toxicity looks at the scientific and technical advancements being made to better optimize drug candidates and accurately predict drug-related toxicities. What assays and models are being used, how physiologically relevant are they, how reliable and predictable is the data, and how is this information translated into knowledge that can impact decision-making? Hear experiences shared by experts and join the interactive sessions and panel discussions for active networking, brainstorming and collaborating.

Recommended All Access Package:27 November: Organ-on-a-Chip and MicroPhysiological Systems27 November Dinner Course: SC2: Understanding Key Concepts in Drug Metabolism and Drug Transport28-29 November: Optimizing Leads and Predicting Drug Toxicity29-30 November: 3D Cellular Models29 November Dinner Course: SC5: Humanized Mouse Models: Technology and Applications in Preclinical Assessment of Cancer Immunotherapy

WEDNESDAY 28 NOVEMBER


INTEGRATING LEAD OPTIMIZATION AND RISK ASSESSMENT STRATEGIES


8:55 Chairperson’s RemarksBernard Faller, PhD, Director, PK Sciences-In vitro ADME, Novartis Institutes for BioMedical Research

9:00 Transport Systems: Victims or Perpetrators in Drug Safety?Bruno Stieger, PhD, Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, SwitzerlandAdverse drug actions are typically caused after the drugs have entered the cells. This is the standard situation, where drug transporting uptake systems act as perpetrators of adverse drug action. Outside of the cells, drug uptake may be impaired by drug-drug interactions and lead to pharmacokinetic drug-drug interactions with uptake systems being victims. At epithelial barriers like the intestine, drugs may interfere with efflux systems, e.g., which become victims. In hepatocytes, drugs or their metabolites can also interfere with the canalicular efflux of bile salts, making BSEP a victim.

9:30 Screening Strategies for Cellular UptakeBernard Faller, PhD, Director, PK Sciences-In vitro ADME, Novartis Institutes for BioMedical ResearchIntra-cellular concentration is an important parameter to assess target engagement, especially for teams working outside the traditional LMW property space where permeability might be rate-limiting. What are the assays that can be used to assess intracellular concentration? How long does one need to incubate? How can one most effectively remove non-specific binding? How are efflux and uptake transporters shifting the equilibrium between medium and intra-cellular compartments?

10:00 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

10:45 Reactive Drug Metabolites in Safety Testing of Novel Drug CandidatesChristine K. Maurer, PhD, Head of Laboratory Discovery Biotransformation, Research & Development, Global Early Development, Merck KGaAMany drugs withdrawn from the market undergo bioactivation to reactive metabolites (RMs). These can form covalent bonds to proteins and/or DNA potentially leading to organ toxicity and/or carcinogenesis. Thus, detection, risk minimization, and integrated risk assessment of RM formation is important in drug discovery and development. In this talk, current methods for RM detection and strategies for risk assessment in oncology projects are discussed in connection with the Merck RM strategy.

11:15 Drug Bioactivation: The Good, The Bad And The UglyAxel Pähler, E.R.T., DMPK/PD Leader, Pharmaceutical Sciences (PS), Roche Pharmaceutical Research and Early Development, Roche Innovation CenterBioactivation is generally considered a risk factor for drug induced toxicities such as DILI. This presentation will highlight cases of reactive metabolite formation linked to safety failures and the key learnings pharma has derived from that. Also highlighted are bioactivation reactions that determine the pharmacological mode of action. In this context learnings from old drug as well as from novel strategies to design selective covalent inhibitors for safe use will be presented.



Cover

Short Courses






3D Cellular Models













11:45 Idiosyncratic Drug Toxicity: Can in silico Tools Predict Bioactivation?John C. L. Erve, PhD, DABT, Consultant, Jerve Scientific Consulting, Inc.Idiosyncratic drug toxicity (IDT) remains a concern to pharmaceutical firms and patients. Bioactivation of drugs to reactive metabolites is integral to the Hapten hypothesis. Bioactivation is traditionally investigated experimentally in vitro together with mass spectrometry. Bioactivation has also be investigated computationally. Approaches include quantum chemical calculations, docking with P450 enzymes and more recently, neural networks. In this talk, in silico approaches will be illustrated using drugs that have caused IDT.


IMPROVING IN VITRO TO IN VIVO TRANSLATION13:45 Chairperson’s RemarksDanilo A. Tagle, PhD, Associate Director for Special Initiatives, National Center for Advancing Translational Sciences, National Institutes of Health

13:50 Use of a Quantitative Systems Pharmacology (QSP) Model to Predict Liver Toxicity in Simulated PopulationsChristina Battista, PhD, Postdoctoral Fellow, University of North Carolina Institute for Drug Safety SciencesDILIsym®, the result of an ongoing public-private partnership, has been developed to investigate drug-induced liver injury (DILI). The model employs mathematical representations of mechanistic interactions following drug administration through the release of serum biomarkers to accurately predict clinical observations in simulated patient populations. This talk will outline DILIsym and discuss applications to date.

14:20 On-/Off-Target and Class Effects of Different Biological Classes and How to Use Them for in silico Modelling of BiologicsAlexander Amberg, PhD, Computational Toxicologist, R&D Preclinical Safety, SanofiA wide variety of biotherapeutic modalities are used as drugs, many of them are a relatively new class of therapeutics. There is an uncertainty regarding the adverse effects of the different biological classes, for some people they are just a result of exaggerated pharmacology. This presentation will summarize results of an analysis of on-/off-target and class effects of different biological classes and will try to answer the question if and how they could be used for in silico modelling approaches of biologics.

14:50 Interactive Breakout Discussion GroupsThis session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas and active networking. Details on the topics and moderators are available on the conference website.

16:00 Refreshment Break in the Exhibit Hall with Poster Viewing

16:45 Microphysiological Systems for Safety and Efficacy StudiesDanilo A. Tagle, PhD, Associate Director for Special Initiatives, National Center for Advancing Translational Sciences, National Institutes of HealthApproximately 30% of drugs have failed in human clinical trials due to adverse reactions despite promising pre-clinical studies, and another 60% fail due to lack of efficacy. The NIH Tissue Chips program is developing alternative approaches

for more reliable readouts of toxicity or efficacy during drug development. Tissue chips are bioengineered microphysiological systems utilizing chip technology and microfluidics that mimic tissue cytoarchitecture and functional units of human organs. These microfabricated devices are useful for modeling human diseases, and for studies in precision medicine and environment exposures.

17:15 Development of Quantitative Systems Pharmacology (QSP) for Improved Association of Preclinical and Clinical Treatment PhenotypesBérengère Dumotier, PhD, Secondary Pharmacology Expert, Safety Pharmacology, Novartis Pharma AGInadequate balance between therapeutic efficacy and adverse events is a major reason for high attrition rates. Majority of adverse events are related to undesirable drug pharmacology (off-target pharmacology, complex pharmacokinetics), and disease-specific pathophysiology of patients. Off-target engagements can be determined at the very early phase of drug discovery processes; however, their translation to AEs is dependent on the two other components mentioned above. The talk will focus on the best way to integrate preclinical and clinical data for small molecules, into a knowledge-based platform for preclinical risk mitigation.

17:45 Immunoallergic HepatitisJürgen Borlak, PhD, Professor, Pharmacology and Toxicology, Institute for Pharmaco- and Toxicogenomics, Hannover Medical SchoolHypersensitivity to NSAIDs may result in serious inflammatory reactions of the liver. We investigated the toxicity of diclofenac in mice, dogs and minipigs and compared findings to clinical DILI cases. I present histopathology and serum/urinary biochemistry findings that were corroborated by immunohistochemistry and immunogenomics. The mechanism of diclofenac-induced immunoallergic hepatitis involves activation of the complement system of the classical and alternate pathway. Thus, an erroneous programing of the innate and adaptive immune system results in granulomatous hepatitis and mastocytosis of the liver.

18:15 Welcome Reception in the Exhibit Hall with Poster Viewing

19:15 Close of Day

THURSDAY 29 NOVEMBER


USE OF STEM CELLS FOR DRUG SAFETY ASSESSMENTS8:25 Chairperson’s RemarksChristopher Goldring, PhD, Senior Lecturer, Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool

8:30 Importance of Phenotyping Your Model to Know What Purpose It Is Fit ForChristopher Goldring, PhD, Senior Lecturer, Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of LiverpoolIt is estimated that 38% and 51% of compounds showing liver injury in man do not show similar effects in animals. The work of the IMI MIP-DILI and TransQST consortia shows how a roadmap is being developed based for the integration of established and emerging test systems and illustrates the increasing complexity



Cover

Short Courses






3D Cellular Models














of models from 2D to multi-cell 3D systems that are used in a logical fashion to assess DILI liabilities of new drugs before they are given to man.

9:00 Bioengineering Human Pluripotent Stem Cell Derived 3D Models for Drug Toxicity and Disease ModelingPaula M. Alves, PhD, Unit Director, Cell Bioprocesses Laboratory, Instituto de Biologia Experimental e Tecnologica (iBET)The development and validation of human in vitro models with physiological relevance, robustness, reproducibility and scalability are still a need in toxicology. Our strategy combines human stem cells, 3D culture strategies and computer-controlled bioreactors in perfusion operation modes. Results concerning the establishment and refinement of culture systems for efficient stem cell differentiation and maturation into cardiac, neural and hepatic cells, as well as their applicability for long-term toxicity testing will be presented and discussed.

Sponsored by9:30 Rethinking the Translational – The use of Highly Predictive hiPSC-Derived Models in Pre-clinical Drug DevelopmentAlexandre Fouassier, Business Development & Sales, Southern Europe, NcardiaCurrent drug development strategies are failing to increase the number of drugs reaching the market. One reason for low success rates is the lack of predictive models. Join our talk to learn how to implement a predictive and translational in vitro disease model, and assays for efficacy screening at any throughput.

10:00 Coffee Break in the Exhibit Hall. Last chance for poster viewing.

10:45 Exploring the Relationship Between Myofilament Calcium and Force Production in the Single iPS-CardiomyocytesMatthew J Daniels MA PhD, MRCP, Wellcome Trust Intermediate Clinical Fellow, Principal Investigator, Division of Cardiovascular Medicine, and BHF Oxbridge Centre of Regenerative Medicine, Oxford UniversityThe in vitro survival of iPS-CMs should aid cardiotoxicity studies of contractility. As contraction depends on depolarisation, both parameters should be measured

in these assays. We find that all classes of chemical dye (voltage, calcium and sodium) impair contractility, and when used in combination with drugs known to act on the myofilament produce confusing composite results making them unreliable for this purpose. We describe how we have overcome this problem.

11:15 Phenotypic Analysis for Cardiotoxicity Evaluation on Human iPSCAnthony Perrier, PhD, Study Director, In vitro Toxicology, Biologie ServierTo improve the early prediction of cardiac toxicity, we developed in vitro tests using High Content Analysis using human iPSC cardiomyocytes. The readouts were qualified using Receiver Operating Characteristic curves and a ranking algorithm was developed to obtain an overall multiparametric cardiotoxicity evaluation for each compound. This cardiotoxicity phenotypic analysis and ensuing improvements will be used for early safety evaluation in the drug development process at Servier.

11:45 Evaluating Cardiovascular Liability and Genetic Disease with hiPSC-CardiomyocytesChris Denning, PhD, Professor and Head, Department of Stem Cell Biology, University of NottinghamWe will review the results from a public-private partnership (NC3Rs-GSK), termed the “CRACK-IT InPulse Challenge” and the software developed to facilitate analysis of cardiac contractility. This sought to evaluate hiPSC-cardiomyocytes in 2D and 3D formats in the blinded evaluation of 28 drugs that were associated with positive or negative inotropy in heart tissue, or no effect. Finally, we will show data on the coupling of hiPSC-CMs and Cas9/CRISPR-mediated gene editing to model hypertrophic cardiomyopathy.

12:15 Brief Session Break

12:20 Bridging Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:50 Close of Conference



Cover

Short Courses






3D Cellular Models











STUDENT FellowshipFull-time graduate students and Ph.D. candidates are encouraged to apply for the World Preclinical Congress Europe Student Fellowship. Applications are due by 19 October 2018.Full-time graduate and PhD candidates qualify for a student rate. Students are encouraged to present a research poster and receive an additional €50 off their registration fee. Students with a research poster will be recognized as a student fellow at the event.

Student rates cannot be combined with any other discount offers. Students must present a valid/current student ID to qualify for the student rate. Limited to the first 100 students that apply.The deadline to submit a poster is 19 October 2018. Those who submit a poster after this date will not receive print recognition in the confer-ence materials.




3rd Annual

3D Cellular ModelsThe Pre-Eminent Discovery Platform

29-30 NOVEMBER 2018



Cover

Short Courses






3D Cellular Models










Unfortunately, investing time, resources and energy into potential therapies, only to see them fail at late-stage clinical trials, is still an all too common occurrence. Inefficiencies in traditional and commonly employed preclinical models are partly to blame for these failures and the ensuing costs that are carried on to payers and end users alike. Thankfully the next generation of 3D Cellular Models is making progress towards predictive safety and efficacy screens that are more relatable to the clinic, though there is still lots to be done in terms of improving their reliability, scalability and reproducibility. Join us for Cambridge Healthtech Institute’s Third Annual 3D Cellular Models, where this promising preclinical model will be explored and evaluated, where future steps towards more accurate and reliable preclinical trials will be taken.



12:30 Registration

12:20 Bridging Luncheon Presentation (Opportunity Available) or Enjoy Lunch on Your Own

12:50 Session Break

IPSC BASED 3D MODELS I13:25 Welcome RemarksJoel Hornby, BSc, Conference Director, Cambridge Healthtech Institute

13:30 Chairperson’s Opening RemarksHansjoerg Keller, PhD, Senior Investigator I, Musculoskeletal, Novartis Institutes for BioMedical Research

13:35 Human Heart-in-a-Jar from iPSC for Disease Modelling and Drug ScreeningRonald A. Li, PhD, Director and Professor, Ming Wai Lau Center for Reparative Medicine, Karolinska InstitutetTraditional drug development is an inefficient and expensive process with unacceptably high failure rates. Major species-specific differences limit the ability of animal models to predict human cardiotoxicity, the dominant reason for attrition. Here, I will present various human ESC/iPSC-derived engineered heart constructs that our group has designed specifically for studying electrophysiology and contractility, including our latest fluid-ejecting “human heart-in-a-jar” that uniquely enables the measurements of clinically complex parameters such as cardiac output, ejection fraction, PV loops.

14:05 An in vitro 3D Kidney Model – Generation and Application in a Pharmaceutical SettingAnna Jonebring, MSc, Senior Scientist, Translational Genomics, Discovery Sciences IMED Biotech Unit, AstraZenecaA disease like chronic kidney disease (CKD), affecting approximately 10% of the population, is one of the areas where there is a great unmet need for innovative pharmacological therapies. Within AstraZeneca we are working with human iPSCs derived 3D kidney models in a platform approach to drive the TI/TV activities as well as developing a highly efficient model for safety/toxicology applications. Combining the 3D model with CRISPR/Cas9, Next-Generation Sequencing (NGS), functional testing and advanced imaging techniques, our 3D kidney platform is evolving and becoming an essential part in our drug discovery process.

Sponsored by14:35 A Novel High-Throughput Multi-Parametric Drug Screening Method for 3D Tumor Spheroids Using Celigo Image CytometerSuzanne Riches, PhD, Technology Research & Development, Manager, Nexcelom Bioscience LLCThere is an increase in utilizing 3D spheroid for drug screening. We demonstrated a cancer drug scoring method using multi-parametric analysis to rank the anti-cancer effects of drugs on tumor spheroids. The assays conducted were growth inhibition, perimeter cell-death, and viability. Drugs can be screened to identify potential drug candidates.

14:50 Sponsored Presentation (Opportunity Available)





WorldPreclinicalEurope.com | 14A Division of Cambridge Innovation Institute


Cover

Short Courses






3D Cellular Models










3D Cellular Models

ADVANCED MODELS FOR DRUG DISCOVERY16:45 Novel 3D Hepatic in vitro Systems for Studies of Chronic Drug Toxicity and Liver DiseaseMagnus Ingelman-Sundberg, PhD, BSc.Med, Professor, Department of Physiology and Pharmacology, Karolinska InstitutetUsing a model of 3D PHH spheroids we observed that drug metabolism was preserved for several weeks of cultivation and that transcriptomic, proteomic and metabolomics analyses revealed similar phenotype as in freshly isolated hepatocytes. In addition, using these 3D spheroid systems we have been able to mimic different liver disease like NAFLD, NASH and fibrosis and found the system suitable for evaluation of mechanisms behind and for identification of drug candidates. In the lecture recent results describing the properties and usefulness of the system will be presented.

17:15 Drug Screening Using Biofabricated 3D Tissue-in-a-Dish ModelsMarc Ferrer, PhD, Team Lead, NIH Chemical Genomics Center, NIH/NCATSAs the success rate from entry into clinical testing to drug approval remains low, 3D tissue models are being developed as alternative in vitro functional assays for drug development. However, the biofabrication of architecturally and physiologically defined human 3D tissue models in a microplate format for drug testing remains a challenge. We will discuss how NCATS is using biofabrication techniques to create a catalog of 3D tissues models for screening.

17:45 Contracting Muscle Models in a Dish for Physiological Drug ScreeningHansjoerg Keller, PhD, Senior Investigator I, Musculoskeletal, Novartis Institutes for BioMedical ResearchThere is a high need for in vitro human microphysiological assay systems in order to enhance the translatability of preclinical drug discovery and development efforts. Using a 3D bioprinting approach, we have developed a new screening platform for the automated fabrication of functional human skeletal muscle tissue models attached between two posts in microwells, which can be electrically stimulated. It is a promising new in vitro exercise model to identify drugs regulating muscle force and fatigue.

18:15 Close of Day and Dinner Short Course Registration

19:00 – 21:30 Recommended Dinner Short Course*SC5: Humanized Mouse Models: Technology and Applications in Preclinical Assessment of Cancer Immunotherapy* Separate registration required, see page 3 for details.

FRIDAY 30 NOVEMBER


IPSC BASED 3D MODELS II8:55 Chairperson’s RemarksMarine Kraus, PhD, Specialist, Group Leader, Stem Cell, Nestle Institute of Health Sciences SA

9:00 Organoids: A Next-Generation in vitro Model That Captures Clinical ResponseLyle Armstrong, PhD, Professor of Cellular Reprogramming & CSO, Newcells Biotech Ltd., Institute of Genetic Medicine, Newcastle UniversityToxicity testing based upon animal models or transformed cell lines is not always an accurate representation of the response of human tissues and organs to xenobiotic substances. The development of human pluripotent stem cells, which are capable of generating many of the cell types found in the adult body, may be an effective solution to address this problem therefore this lecture will attempt to present not only the background of what pluripotent stem cells are and how they are made but also how we can use them to produce versatile new toxicity assays for use in pharmaceutical development.

9:30 In vitro Generation of Functionally Mature Beta-Cells from Adult Human iPSCsMarine Kraus, PhD, Specialist, Group Leader, Stem Cell, Nestle Institute of Health Sciences SAIslet transplantation has demonstrated that replacement of the beta-cell mass in diabetic patients is able to restore endogenous glycaemic control. Stem-cell therapies hold great promise for generating a replenishable supply of insulin producing beta-cells for transplantation. In the present studies, we report the in vitro generation of functionally mature beta-cells from human iPSCs. These newly generated beta-cells display mature features and exhibit glucose regulated insulin secretion, displaying the first and second insulin release phases characteristic of human islets.


STEM CELL BASED 3D MODELS10:45 Engineered Fail-Safe and Allo-Tolerated 3D Tissue for in situ Drug Manufacturing and Delivery to Treat DiseaseAndras Nagy, PhD, Senior Investigator, Lunenfeld-Tanenbaum Research Institute, Sinai Health SystemPluripotent Stem cells have accelerated the development of new avenues for targeting diseases with cell therapies. Numerous of these are currently on their way. We addressed two significant hurdles of cell therapies; safety and long-term allograft tolerance without immune suppression. The combination of these two allows the generation of stable allogeneic 3D tissues which could be a source of secreted biologics to treat diseases, for example, endocrine and metabolic deficiencies.

11:15 Modeling Kidney Development and Disease through 3D OrganoidsNuria Montserrat, PhD, Group Leader, Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC)Our aim is to facilitate basic knowledge on kidney engineering providing novel approaches facilitating renal maturation and function. We have generated kidney organoids from human pluripotent stem cells. In parallel, we have developed biomimetic inks for bioprinting 3D kidney structures. Lastly, using a novel transplantation method we have further maturated and vascularized kidney organoids. We provide innovative solutions when translating these technologies into the clinical setting.





Cover

Short Courses






3D Cellular Models










3D Cellular Models

11:45 Organoids: A Next-Generation in vitro Model That Captures Clinical ResponseRobert Vries, PhD, Managing Director, Stichting Hubrecht Organoid TechnologiesThe laboratory of Hans Clevers, the founder of HUB, previously discovered the identity of adult stem cells in many human tissues such as intestine and liver (Barker et al., Nature 2007; Huch et al., Nature 2013). More recently, we were able to demonstrate that the in vitro response of organoids directly correlates with the clinical outcome of the patient from which the organoid was derived (Dekkers et al., Sci Trans Med 2016; Sachs et al., Cell 2018). In addition, we have now developed a novel system that allows the co-culture of organoids with immune cells to study the effect of immune modulating drugs.


COMPLEX CELL SYSTEMS13:40 Chairperson’s RemarksGlyn N. Stacey, PhD, CEO, International Stem Cell Banking Initiative

13:45 Quality Control and Standardisation for Complex Cell SystemsGlyn N. Stacey, PhD, CEO, International Stem Cell Banking InitiativeThe use of cell cultures requires attention to identity of starting cells, awareness of potential contamination and attention to accurate documentation of reagents, cell sources and protocols (Coecke et el., 2005). A further development of this best practice guidance will be described is being led by the Centre for Alternatives to Animal Testing and incorporates pluripotent stem cell culture, 3D cultures and tissue on a chip systems (Pamies et al., 2016).

14:15 3D Spheroids: Bridging the Gap Between In Vitro and In VivoSakshi Garg, PhD, Head of laboratory, Discovery Pharmacology, Merck KGaAOver the last decades, data has emerged highlighting that conventional 2D cell culture tumor models fail to capture important aspects of tumor physiology. The predictive value of phenotypic screening is directly correlated to how closely the chosen assay represents the in vivo conditions. To mimic the cell physiology and biological characteristics of tumors we use 3D cellular spheroids combined with a co-culture system to recapture the tumor microenvironment better.

14:45 The Phenion Full Thickness Skin Model: A Versatile Tool for Efficacy and Toxicological Testing of Dermally Applied CompoundsDirk Petersohn, PhD, Director, Beauty Care Technologies - Biological & Clinical Research, Henkel AG & Co. KGaASkin is often the site of first contact for many substances. The Phenion® Full Thickness skin models mimic native human skin in its histology and a wide spectrum of biochemical properties. Primary human keratinocytes form a fully differentiated epidermis that connects through the basement membrane with the underlying collagenous dermis that is populated with fibroblasts of the same donor. Its biological equivalence with human skin makes the tissue model perfectly suited for efficacy testing of substances or toxicological assessments, as exemplified with the 3D-Skin Comet assay.

15:15 aProximate™ in vitro Renal Proximal Tubule Cell Model and Clinically Relevant Biomarkers as a Predictive Screening Platform to Understand NephrotoxicityColin Brown, PhD, Associate Professor at Institute of Cell & Molecular Biosciences, Medical School, Newcells Biotechnology, Newcastle UniversityWe have developed a series of in vitro primary renal proximal tubule models as a platform to understand the proximal tubule handling of drug molecules and to screen drug molecules for nephrotoxic potential using clinically relevant biomarkers of renal damage. We have now characterised a new 3D-multilayer model of the proximal tubule including proximal tubule cells, interstitial fibroblasts and endothelial cells which may improve differentiation and longevity in culture further.





3rd Annual

Preclinical Models for Cancer Immunotherapy and Combinations Strategy and Technology for Translational IO

28-29 NOVEMBER 2018



Cover

Short Courses






3D Cellular Models










The selection of appropriate preclinical models based on similarity to human biology and disease genotype and phenotype carries considerable potential to ensure higher predictability of preclinical trials. The design and interpretation of first-in-man trials remains a major challenge in the development of novel anticancer agents. Key study design elements such as schedule, escalation strategy, targeted patient population, etc. rely heavily on preclinical (usually in vivo) data. This situation brings into question the predictability of preclinical tumor models, as well as the method of analysis and translation of the results of preclinical studies. It is especially difficult to model for preclinical assessment of cancer immunotherapy, the most actively developing area in oncology. The need for simulating the response of the immune system adds to the complexity of preclinical models and their applications. Cambridge Healthtech Institute’s Third Annual Preclinical Models for Cancer Immunotherapy and Combinations conference aims to bring together cancer researchers and clinicians in order to initiate knowledge and opinion exchange around predictability of preclinical tumor models, including immunocompetent models, and the strategies for preclinical design and assessment of cancer immunotherapy and combination therapy.

Recommended All Access Package:27 November: Single-Cell Analysis27 November Dinner Course: SC3: The Origins, Optimization and Application of Organ-on-a-Chip Systems28-29 November: Preclinical Models for Cancer Immunotherapy and Combinations29-30 November: Translational Biomarkers in Immuno-Oncology29 November Dinner Course: SC5: Humanized Mouse Models: Technology and Applications in Preclinical Assessment of Cancer Immunotherapy



NON-CLINICAL APPROACHES TO PREDICT COMBINATION VALUE

8:20 Welcome RemarksMarina Filshtinsky, Executive Director, Cambridge Healthtech Institute

8:25 Chairperson’s RemarksSara Colombetti, PhD, Head of Oncology Discovery Pharmacology, Roche Innovation Center Zürich

8:30 Immunotherapy Combination: How Can Preclinical Models Guide the Selection of the Best Combo PartnerSara Colombetti, PhD, Head of Oncology Discovery Pharmacology, Roche Innovation Center ZürichPreclinical mouse models are key tools to evaluate the activity of cancer immunotherapies. They are instrumental to understanding the mechanism of action of tested compounds, and help with identifying rationale combination partners for best anti-tumor efficacy. We show here how the Pharmacology Group at the Roche Innovation Center Zurich has been developing over the past years a cutting edge mouse models platform for in vivo profiling of immunotherapies and their combinations.

9:00 Maximizing Therapeutic Index of the PI3K Inhibitor Alpelisib Using Selective Circadian TimingMichael Rugaard Jensen, PhD, Director, Head of ONC Discovery Pharmacology Basel, Novartis Institutes for BioMedical ResearchClinically, the PI3K inhibitor alpelisib (NVP-BYL719) is facing on-target tolerability challenges (hyperglycemia) that limit the dose administered in the morning. As glucose metabolism is highly regulated by circadian rhythms, an integrative circadian-timing approach was adopted in preclinical models. Using radio-telemetry technology, real time blood glucose levels were recorded in freely moving rats at different dosing regimens. Based on results from these preclinical studies, a clinical treatment schedule predicted to increase therapeutic index is being explored.

Sponsored by9:30 Checkpoint Inhibitors Efficacy Assessment in Immunocompetent Preclinical Models Featuring Human Immune CheckpointsKader Thiam, Vice President, Transgenic Technologies, genOwaygenOway developed a pipeline of immuno-competent mouse expressing humanized immune check-point for pre-clinical immunotherapies studies (PD-1, VISTA, GITR, SIRPa, OX40, CTLA-4, Tim3...). Validation studies confirmed that humanized targets behave as its mouse counterpart and models allow in vivo assessment of human ICP targeting compounds.

Sponsored by9:45 The Hollow Fiber Model – Testing Drug Efficacy Against Three Cancer Cell Lines in One Mouse? Yes, We Can!Bettina Stahnke, PhD, Business Development, ProQinaseIdentifying the best tumor model and best drug to proceed with is a challenge for every cancer drug discovery process. The Hollow Fiber Model allows to test a given drug on three cell lines simultaneously in each mouse, providing an economic way to explore multiple treatment options in short time.






Cover

Short Courses






3D Cellular Models











ASSESSING IMMUNOMODULATORY ANTIBODIES10:45 Preclinical Modelling of Immune-Oncology Therapies: Challenges and SolutionsKelli Ryan, PhD, Senior Scientist, Oncology Department, MedImmuneMedimmune is a leading global biologics R&D company with a strong track record of discovering novel immunotherapies for cancer treatment. Over the last several years, we have generated extensive preclinical pharmacology packages to support transition of multiple drug candidates into clinical phase. Our pipeline includes therapies with diverse mechanisms of action and novel platforms each of which have posed a unique set of in vivo challenges to deliver essential in vivo pharmacology data for project progression. Presented here will be an overview of some of these challenges and the ways in which we responded to overcome those challenges, including characterization of syngeneic models, and adaptations of our models and study designs to answer specific pharmacology and mechanistic questions. By doing so, we demonstrate the utility of our approaches to preclinical pharmacology to support project progression despite the increasing complexity of our drug modalities.

11:15 Combining STING Agonists with an Anti-PD-1 Antibody Results in Marked Anti-Tumor Activity in Poorly Immune-Infiltrated Tumor ModelsSamanthi A. Perera, PhD, Associate Principal Scientist, Merck & Co. Inc.We synthesized a novel STING agonist that activates both mouse and human STING with higher in vitro potency than cGAMP. The STING agonist was administered to immune-competent mice bearing MC38 syngeneic tumors to monitor pharmacodynamics, pharmacokinetics and in vivo efficacy. Intratumoral doses provided complete responses in 100% tumors. Tumor models such as CT26 and B16-F10 that are intrinsically resistant to single-agent therapy with anti-PD-1 antibody also demonstrated long-term tumor regressions.

Sponsored by11:45 Meet the Nanoimager, The Next Generation Platform for Preclinical Studies Mariya Georgieva, PhD, Business Development, ONIQuantitative imaging techniques are powerful tools enhancing the predictability and reliability of pre-clinical models for drug discovery and target validation. ONI crafts desktop-compatible instruments with single-molecule sensitivity allowing for direct observation and measurement of molecular interactions, cellular dynamics and complex tissue phenotypes.


T-CELL THERAPY DESIGN AND PRECLINICAL ASSESSMENT13:45 Chairperson’s RemarksMarc Davies, PhD, CAR Mechanics Laboratory, Research Oncology, Division of Cancer Studies, King’s College London

13:50 Selected Poster Presentation: A Highly Tumor-Specific T Cell Engaging Bispecific Antibody Targeting TA-MUC1 Induces Strong T Cell Infiltration in 3D MCF-7 Tumor SpheroidsTimo Lischke, PhD, Scientist, Preclinical Pharmacology & Cancer Immunology, GLYCOTOPE GmbH

14:00 Selected Poster Presentation: Anti-Tumor Efficacy of Anti-GITR in Preclinical hGITR ModelKader Thiam, Vice President, Transgenic Technologies, Director Business Development, genOway

14:10 Selected Poster Presentation: New Spontaneous and Carcinogen Induced Mouse Derived Isograft (MDI) Tumor Models for Drug Development of Novel Immune Therapeutic ApproachesBettina Stahnke, PhD, Business Development, ProQinase

14:20 Generation of Chimeric Antigen Receptor (CAR) T-Cells for Solid MalignanciesMarc Davies, PhD, CAR Mechanics Laboratory, Research Oncology, Division of Cancer Studies, King’s College LondonDespite demonstrating unparalleled responses in the treatment of B-cell and plasma cell malignancies, Chimeric Antigen Receptor (CAR) T-cells have had a more modest response against solid malignancies. This talk will focus on the successful generation of CAR T-cells against a variety of target antigens expressed in solid malignancies and the translation of one of these CAR into a first-in-man Phase I clinical trial.



PATIENT DERIVED ORGANOIDS FOR PERSONALIZED IO16:45 Patient-Derived 3D Microtumors (PDMs) – A Versatile Platform for Compound Profiling and Efficacy Testing in Precision OncologyChristian Schmees, PhD, Head of Tumor Biology, Molecular Biology Department, NMI Natural and Medical Sciences Institute at the University of TübingenA significant aspect of personalized cancer treatment is the integration of clinical with molecular data including multi-omics and functional analyses to assess individual signaling perturbations as vulnerabilities to tailored therapy. Patient-derived ex vivo models enable the implementation of this concept within a clinically relevant time frame. I will introduce our PDM platform co-cultured with autologous tumor-infiltrating lymphocytes (established for 11 human cancer types), and present data from transcriptomic and proteomic profiling as well as compound testing using chemo- and immunotherapeutics, and small molecules.

17:15 Patient-Derived Organoids: Promises, Hurdles and Potential Clinical ApplicationsSomaieh Hedayat, PhD Student, Molecular Pathology, Institute of Cancer ResearchPatient-derived organoids (PDOs) have recently emerged as robust preclinical models. We have recently shown that PDOs from metastatic, heavily pretreated, colorectal and gastroesophageal cancer patients mirror the phenotype and the genotype of their parental biopses and recapitulate clinical responses observed in patients. The combined use of PDOs, PDO-xenotransplants and ex vivo PDO co-cultures has the potential to accelerate drug discovery and improve patients’ selection in early phase clinical trials.





Cover

Short Courses






3D Cellular Models











17:45 CO-PRESENTATION: 3D-3-Culture: A Tool to Unveil Macrophage Plasticity in Tumor MicroenvironmentCatarina Brito, PhD, Lab Head, Advanced Cell Models Lab, Animal Cell Technology Unit, iBET - Instituto de Biologia Experimental e Tecnológica; ITQB-NOVACatarina Pinto, Postdoctoral Fellow, Advanced Cell Models Lab, Animal Cell Technology Unit, iBET - Instituto de Biologia Experimental e Tecnológica; ITQB-NOVAWe have been exploring culture platforms based on alginate microencapsulation and stirred culture systems to develop tools to study macrophage plasticity in response to therapy. In 3D-3-cultures (co-culture of tumor cell spheroids, fibroblasts and monocytes), features of immunosuppressive cancer microenvironments are recapitulated. We have observed accumulation of cytokines, ECM and metalloproteinases, with infiltration of macrophages in the tumor mass and trans-polarization into M2-like phenotypes. Challenging of the system with therapeutic compounds induced modulation of the M2-like phenotype.


19:15 Close of Day



CRISPR-BASED TUMOR MODELING8:25 Chairperson’s RemarksAnita Seshire, PhD, Lab Head, Cellular Pharmacology, Translational Innovation Platform Oncology, Merck KGaA

8:30 CRISPR-Based Models in Drug Discovery: Developments, Caveats and Future PerspectivesDanilo Maddalo, PhD, Lab Head, ONC Pharmacology, Novartis Institutes for BioMedical Research, Novartis Pharma AGThe development and the application of genome editing techniques in vivo has expanded the toolkit of preclinical models to assess drug efficacy and toxicology as well as the effect of compounds on tumour-microenvironment interaction. Cost- and time-efficient, the talk will give an overview of CRISPR models, how they impacted significantly the workflow of preclinical drug discovery and their limitations and caveats.

9:00 Modelling Pancreatic Cancer Subtypes and Immunosuppressive Tumor Microenvironments by Genome Engineering in MiceDieter Saur, Professor of Molecular Biology, Technical University of MunichWe generated novel PDAC models that permit spatial and temporal control of gene expression and modelling of PDAC subtypes and their respective microenvironments. These tools provide unparalleled access to the native biology of cancer cells and their hosting stroma, and rigorous genetic validation of candidate therapeutic targets in autochthonous tumours and subtype specific drivers in the immune system.

Sponsored by9:30 Utilization of New Humanized Mouse Models to Better Understand Emerging Immunomodulation TherapiesJames G. Keck, PhD, Senior Director, Innovation & Product Development, In Vivo Services, The Jackson LaboratoryThe JAX® Onco-Hu® platform utilizes humanized mice engrafted with tumors to enable in vivo investigation of the interactions between the human immune system and human cancer. Next generation humanized NSG strains with potential for immune-oncology research will be presented and will include the NSG-SGM3, which produces human T and myeloid cells, NSG-HLA A2, a transgenic mouse that allows HLA class I autologous studies and the NSG-IL15 transgenic which produces T and natural killer cells.


SUMMARY SESSION: RECENT ADVANCES IN PRECLINICAL IO10:45 Utilizing 3D Models for Cancer Stem Cell Target Validation and Drug DiscoveryAnita Seshire, PhD, Lab Head, Cellular Pharmacology, Translational Innovation Platform Oncology, Merck KGaATumor spheres are three-dimensional structures that spontaneously form under non-adherent and serum free conditions. Sphere formation is an exclusive function of tumor initiating cells (cancer stem cells). We show how to utilize 3D-spheres for in vitro and in vivo models for therapeutic antibody validation.

11:15 Targeting CD47 in Cancer with Bispecifc AntibodiesKrzysztof Masternak, PhD, Head of Biology, Novimmune SATo evade the immune system, cancer cells hijack CD47, a ubiquitously expressed marker of “self” that healthy cells display to macrophages and DCs to transmit a “don’t eat me” signal. Dual-targeting bispecific antibodies allow for selective, tumor-directed CD47 blockade, enhancement of antibody directed tumor cell phagocytosis and antigen cross-presentation, and strong anti-tumor responses in vivo.

11:45 Preclinical Characterization of BiTE® Antibody Constructs for the Treatment of Hematological MalignanciesPetra Deegen, Senior Scientist, Nonclinical Safety Sciences within Comparative Biology & Safety Sciences (CBSS), AMGEN Research (Munich) GmbHUnderstanding approaches to validate new BiTE constructs nonclinically are important to lay a robust path to the clinic. This presentation will cover in vitro and in vivo studies supporting clinical development of a BiTE antibody construct for the treatment of multiple myeloma.





Inaugural

Translational Biomarkers in Immuno-OncologyIdentifying Mechanism-of-Action and Patient Population

29-30 NOVEMBER 2018



Cover

Short Courses






3D Cellular Models










Challenges in discovering predictive biomarkers for cancer immunotherapy involve multiple cell types, multiple mechanisms of T-cell regulation, genetic heterogeneity of tumors, immune components, etc. At the same time, biomarker strategies are shaping the current state of immuno-oncology, and will become increasingly important. Cambridge Healthtech Institute’s Inaugural Translational Biomarkers in Immuno-Oncology conference is designed to bring together researchers from pharmaceutical companies, preclinical and clinical biomarker CROs, and laboratory medicine community to discuss the underlying mechanisms of cancer immunotherapy, exploratory and translational biomarkers, emerging clinical assays aiming to advance new agents discovery and development and to improve patient outcomes.

Recommended All Access Package:27 November: Single-Cell Analysis27 November Dinner Course: SC3: The Origins, Optimization and Application of Organ-on-a-Chip Systems28-29 November: Preclinical Models for Cancer Immunotherapy and Combinations29-30 November: Translational Biomarkers in Immuno-Oncology29 November Dinner Course: SC5: Humanized Mouse Models: Technology and Applications in Preclinical Assessment of Cancer Immunotherapy


12:30 Registration

BIOMARKERS TO GUIDE COMBINATION THERAPY DESIGN AND DEVELOPMENT

13:25 Welcome RemarksMarina Filshtinsky, Executive Director, Cambridge Healthtech Institute

13:30 Chairperson’s Opening RemarksJennifer Mataraza, PhD, Group Lead, Translational Immuno-Oncology, Novartis Institutes of Biomedical Research

13:35 Advancing Immuno-oncology Combinations in the Clinic: Lessons from Mice and MenJennifer Mataraza, PhD, Group Lead, Translational Immuno-Oncology, Novartis Institutes of Biomedical ResearchImmune checkpoint blockade therapies are revolutionizing the standard cancer treatment. Despite the current success of anti-PD1/PDL1 therapies, not all patients respond. Combination approaches are the keys to improving clinical response. Macrophage targeting therapies are an attractive combination partner for anti-PD-1 pathway blockade; this is currently being tested in the ongoing Phase Ib/II study of Lacnotuzumab (anti-CSF-1) and Spartalizumab (anti-PD-1) in patients with advanced solid tumors. Emerging efficacy and biomarker data will be presented.

14:05 Biomarker Discovery and Translational Immune-Oncology: Use of Human Tissue-Based Models in Preclinical Research Svetlana Sadekova, Senior Principal Scientist, Head of Translational Pathology Group, MerckRapid advancement of immuno-oncology is creating the need for translational strategies to guide indication selection, understand mechanisms of resistance and identify biomarkers of response. This talk will highlight the importance of understanding human tumor microenvironment and focus on strategies based on utilizing human tissues for preclinical and clinical translational research.

14:35 Pathologist Involvement in Image Analysis Powered Biomarker Quantification Abraham Silva Carmona, Pathologist, Definiens, Subsidiary of Medimmune/ AstraZenecaImage analysis based quantification of immunohistochemical biomarkers is a powerful method supporting both the preclinical as well as the clinical area of drug development by enabling the analysis of spatial relationships between different cell populations. To leverage the full potential of image analysis and provide the best quality data the pathologist should be involved in every step of the process.



INNOVATIVE APPROACHES: ROCHE-GENENTECH SESSION16:45 Leveraging Concomitant Medications Data for in silico Phase Ib Clinical TrialsMatthew Albert, MD, PhD, Principal Scientist, Cancer Immunology, GenentechA standardized approach to the assessment of pathologic response is necessary for reliable interpretation of the post-treatment resection specimens in patients receiving neoadjuvant anti-PD-1 therapy. Neoadjuvant specimens also provide a unique window into the mechanism of action of immune checkpoint blockade. The features of immune-mediated tumor clearance will be described, and a provisional,





Cover

Short Courses






3D Cellular Models











reproducible scoring system for pathologic response to neoadjuvant anti-PD-1 based on these features will be presented.

17:15 Factors That Influence Circadian Rhythm of Endogenous Biomarker Kynurenine (Kyn) and Tryptophan(Trp)Richard (Xu) Zang, PhD, DMPK, GenentechKynurenine (Kyn) and tryptophan (Trp) are well studied biomarkers for the regulatory and functional aspects of Trp 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) enzyme. The Kyn and Trp pathway has been a target of high interest as any dysregulation or overactivation of this pathway could be associated with immune system related pathologies. Our results indicated that there is a circadian rhythm of the basal level of Kyn and Trp concentration. Various intrinsic and external factors that could influence the basal level fluctuation of Kyn and Trp concentration were indentified. Pharmacodynamic modeling efforts were employed to quantitatively describe the circadian rhythm of Kyn and Trp in preclinical animal models.

17:45 PANEL DISCUSSION: Exploratory and Translational Biomarkers in IO: Evolutionary Approach Moderator: Matthew Albert, MD, PhD, Principal Scientist, Cancer Immunology, GenentechPanelists: Jennifer Mataraza, PhD, Group Lead, Translational Immuno-Oncology, Novartis Institutes of Biomedical ResearchSvetlana Sadekova, Senior Principal Scientist, Head of Translational Pathology Group, MerckRichard (Xu) Zang, PhD, DMPK, Genentech



FRIDAY 30 NOVEMBER


TUMOR MICROENVIRONMENT: BIOMARKERS AND TARGETS8:55 Chairperson’s RemarksSvetlana Sadekova, Senior Principal Scientist, Head of Translational Pathology Group, Merck

9:00 Immunological Determinants of Response to Neoadjuvant Chemotherapy in Breast CancerSofia Braga, MD, PhD, Assistant Professor, Instituto CUF Oncologia, NOVA Medical SchoolNeoadjuvant chemotherapy is the treatment option for locally advanced breast cancer. However, more than half of the patients do not respond. We need clinical biomarkers that could predict treatment response. Tumor infiltrating lymphocytes, CD8+ and Tregs, are being studied. Nonetheless, tumor cells can escape the immune system by releasing cytokines or expressing immune checkpoint

inhibitors. T cell activation markers could be reliable biomarkers of response reflecting the tumor immune environment.

9:30 Translating Breast Cancer Immune Features into Putative Biomarkers: HLA-DR in Cytotoxic T Lymphocytes Predicts the Response to Neoadjuvant Chemotherapy Maria Guadalupe Cabral, PhD, Invited Assistant Professor, CEDOC/NOVA Medical School – Faculdade de Ciências Médicas/Universidade NOVA de LisboaPrediction of breast cancer response to Neoadjuvant Chemotherapy (NACT) is needed to promptly direct non-responders to alternative therapies. It has been suggested that efficacy of chemotherapy relies on infiltrating lymphocytes but considering that lymphocytes activity could be spoiled by the tumor, their presence per se has a modest prognostic value. We disclosed that the activation of Cytotoxic T lymphocytes, revealed by HLA-DR expression, is a more attractive predictor of NACT-response.


NANOTECHNOLOGY FOR IO BIOMARKER RESEARCH10:45 Meet the Nanoimager, the Next Generation Platform for Enhanced Biomarker DiscoveryMariya Georgieva, PhD, Business Development, Oxford Nanoimaging (ONI)Quantitative imaging techniques are powerful tools enhancing the predictability and reliability of pre-clinical models for drug discovery and target validation. With a mission to significantly enhance the performance and accelerate biomarker discovery pipelines, ONI provides the drug discovery sector with desktop-compatible instruments capable of single-molecule sensitivity allowing for direct observation and measurement of molecular interactions, cellular dynamics and complex tissue phenotypes.

11:15 Selected Poster Presentation: Versatile Dendritic Nanoparticles for Immunotherapy, Gene Delivery, and Controlled Tumor PenetrationSeungpyo Hong, PhD, Professor, Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin - Madison; Director, Wisconsin Center for NanoBioSystems (WisCNano)Dendritic polymers have drawn considerable attention to be used as a nanocarrier platform for various therapeutic agents over the past few decades. Major advantages of the macromolecules include: i) the ability to mediate strong multivalent binding; ii) efficient, controlled tumor penetration due to their sub 10 nm size and deformability; and iii) facile multifunctionalization through various conjugation chemistries. In this presentation, our recent efforts on using poly(amidoamine) (PAMAM) dendrimers for immunotherapy and miRNA delivery will be summarized.

11:45 KEYNOTE PRESENTATION: Cancer Metastasis and Liquid BiopsyKlaus Pantel, MD, Director, Institute of Tumor Biology, University Hospital Hamburg-EppendorfFunctional characterization of CTCs using specialized in vitro and in vivo test systems has started, which might provide novel insights into the biology of metastatic tumor cells and serve as models for drug testing. New blood-based biomarkers currently validated in clinical trials include miRNAs, exosomes and tumor-educated platelets.





Cover

Short Courses






3D Cellular Models











12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Session Break

LIQUID-BIOPSY BASED BIOMARKERS 13:40 Chairperson’s RemarksEd Schuuring, PhD, Head of the Laboratory for Molecular Pathology, Senior Clinical Scientist of Molecular Pathology, Department of Pathology, University Medical Center Groningen

13:45 Functional Analyses of Circulating Tumor Cells in Cancer PatientsCatherine Alix-Panabières, PhD, Director, Laboratory Detection of Rare Human Circulating Cells (LCCRH), University Medical Centre of MontpellierCirculating tumor cells (CTCs) in blood are promising new biomarkers potentially useful for prognostic prediction and monitoring of therapies in patients with solid tumors. CTC-research opens a new avenue for understanding the biology of metastasis in cancer patients. As an in-depth investigation of CTCs is hampered by their low number, the establishment of cell-cultures and permanent cell lines from CTCs has become the most challenging task over the past year.

14:15 Epigenetic Alterations in CTCs and Corresponding ctDNAEvi Lianidou, PhD, Professor of Analytical Chemistry – Clinical Chemistry, Laboratory of Analytical Chemistry, Analysis of Circulating Tumor Cells (ACTC) Lab, Department of Chemistry, National and Kapodistrian University of AthensOur group was the first to demonstrate epigenetic alterations in CTCs and corresponding ctDNA (Chimonidou et al., Clin Chem 2011, Clin Chem 2013). Epigenetic silencing of estrogen receptor gene (ESR1) could be of clinical relevance especially for its potential impact on endocrine treatment efficacy. In this study, we evaluated for the first time ESR1 methylation in CTCs, paired ctDNA and primary tumors of breast cancer patients.

14:45 ctDNA as a Biomarker for Early Tumor Response Assessment in Lung Cancer Patients Treated with ImmunotherapyEd Schuuring, PhD, Head of the Laboratory for Molecular Pathology, Senior Clinical Scientist of Molecular Pathology, Department of Pathology, University Medical Center GroningenCurrently, we are not able to reliably predict which patients benefit from immune checkpoint inhibitors (iCPI). PD-L1 tumor expression levels (among others) are not reliable predictors for the individual response to iCPI. The aim of this study was to assess changes of ctDNA levels in cell-free plasma during therapy as an early response biomarker and a monitoring tool for durable responses to immunotherapy in KRAS/BRAF mutated advanced NSCLC.

15:15 PANEL DISCUSSION: Developing Circulating Biomarkers for Clinical ResaerchModerator: Evi Lianidou, PhD, Professor of Analytical Chemistry – Clinical Chemistry, Laboratory of Analytical Chemistry, Analysis of Circulating Tumor Cells (ACTC) Lab, Department of Chemistry, National and Kapodistrian University of Athens• Prognostic vs. Predictive Markers: Where is the clinical utility?• Do CTC platforms matter?• Automated vs. observer-dependent calls: advantages and disadvantages• How can we best incorporate circulating biomarkers into clinical trials?





Inaugural

Target Identification & Validation StrategiesExploring Functional Genomics, Chemical Biology & Phenotypic Screening

28-29 NOVEMBER 2018



Cover

Short Courses






3D Cellular Models










Finding novel, druggable targets for therapeutic intervention remains a top priority for the pharma/biotech industry, especially when it comes to building a robust drug discovery pipeline. It also remains a formidable challenge and companies continue to invest a lot of time and resources in identifying and validating good drug targets to pursue. What are the challenges in target discovery? What tools and strategies are being used and how well are they working? What’s being done to ensure that validated targets lead to better and safer therapies? Cambridge Healthtech Institute’s conference on Target Identification and Validation Strategies will bring together leading experts to discuss some of these critical questions. The talks will highlight how functional genomics, phenotypic screening and chemical biology can be used to find new drug targets, validate existing targets for new indications, and better understand how inhibiting or activating these targets could impact cellular pathways. The conference will help attendees meet and interact with experts and peers from around the world to share ideas and hear about new strategies and technologies helping target discovery.

Recommended All Access Package:27 November: Artificial Intelligence and Machine Learning for Drug Discovery27 November Dinner Course: SC3: The Origins, Optimization and Application of Organ-on-a-Chip Systems28-29 November: Target Identification and Validation Strategies29-30 November: CNS Models and Translational Strategies29 November Dinner Course: SC5: Humanized Mouse Models: Technology and Applications in Preclinical Assessment of Cancer Immunotherapy



USE OF CRISPR, RNAi, AND OTHER FUNCTIONAL GENOMIC SCREENS FOR FINDING NOVEL TARGETS


8:55 Chairperson’s RemarksJohn Doench, Ph.D., Associate Director, Genetic Perturbation Platform, Broad Institute of Harvard and MIT

8:30 Up, Down, and Out: Multiplexing CRISPR Modalities for Genetic ScreensJohn Doench, PhD, Associate Director, Genetic Perturbation Platform, Broad Institute of Harvard and MITThe ease of programming Cas9 with an sgRNA presents an abundance of potential target sites, but the on-target activity and off-target effects of individual sgRNAs can vary. We will discuss the design and use of libraries for CRISPR-based knockout screens, activation (CRISPRa) and interference (CRISPRi) technologies, and combinatorial approaches.

9:30 Unbiased Compound-Target Interface Mapping through Forward GeneticsMoritz Horn, PhD, Postdoctoral Fellow, Laboratory of Dr. Martin Denzel, Max Planck Institute for Biology of AgeingWe present a chemical mutagenesis approach to map compound binding interfaces in forward genetic screens and exemplify this for several compounds. We leverage haploid embryonic stem cells as genetic tool to reveal loss-of-function, gain-of-function, and separation-of-function mutations, since chemical mutagenesis in haploid cells can uncover recessive traits. In summary, chemical mutagenesis combined with deep sequencing allows to identify drug targets at amino acid resolution in an unbiased genome-wide scale.


10:45 Geometry and Genome Editing: A Comparative Analysis of Targeted siRNA and CRISPR Arrayed Screens in 3DMadhu Lal-Nag, PhD, Group Leader, Trans-NIH RNAi Facility, National Center for Advancing Translational Sciences, National Institutes of HealthThe recent emergence of CRISPR/Cas9-based technologies has led to the development of several orthogonal approaches for functional genomic screening that complement or improve upon existing RNAi screening approaches. Thus far, CRISPR screens have been mostly performed within an individual laboratory setting where expertise exists, for example, those employing a pooled library approach with a simple phenotype such as cell survival. However, here we describe the development of a robust, reproducible, and flexible CRISPR/Cas9-based high-throughput screening (HTS) workflow that is compatible with the assessment of more complex phenotypic assays.

11:15 CRISPR-UMI: Single Cell Lineage Tracing of Pooled CRISPR/Cas9 ScreensUlrich Elling, PhD, Principle Investigator, Institute of Molecular Biotechnology Austria (IMBA)





Cover

Short Courses






3D Cellular Models












EXPLORING VARIOUS MODELS, ASSAYS AND PLATFORMS FOR PHENOTYPIC SCREENING

13:45 Chairperson’s RemarksUlrich Elling, PhD, Principle Investigator, Institute of Molecular Biotechnology Austria (IMBA)

13:50 Filling the Drug Discovery Gap: Is High-Content Screening the Missing Link?Jean-Philippe Stephan, PhD, Director Servier Center of Excellence Pharmacological Screening, Compound Management and Biobanking, Institut de Recherches ServierThe pharmaceutical industry is now implementing new discovery paradigms to try to solve the current disconnect between drug discovery and human clinical trials. High-Content Screening (HCS) combined with biosensors, genome-editing and stem cell-derived cellular models offer the opportunity to drastically transform phenotypic screening, linking target engagement and phenotypic impacts in more relevant in vitro models. Despite the tremendous potential of HCS, researchers have to carefully consider various aspects before deploying the technology and this presentation will go through several examples highlighting the current strengths and weaknesses of the approach.

14:20 Target Deconvolution and Validation Strategies for Antibodies from Target-Agnostic Phenotypic ScreensAlan Sandercock, PhD, Scientist II, Department of Antibody Discovery and Protein Engineering, MedImmunePhenotypic screening methods can be applied to biological drug discovery to find novel functional targets and, in some cases, drug leads direct from target-agnostic screens. Target identification is often challenging, but is vital for characterising and developing a therapeutic antibody. The subsequent path from target ID to validation can be long, especially where poorly understood biological pathways are encountered. Here, we will describe how our approaches have evolved to allow phenotypic screening to supplement a target-led biologics portfolio.



16:45 A High Density CRISPR Tiling Mutagenesis Genetic Screen for Target DeconvolutionDirk Daelemans, PhD, Associate Professor, Rega Institute - Laboratory of Virology and Chemotherapy, KU LeuvenDeconvoluting the direct molecular target of hits from a complex phentotypic high-throughput screen or validating the target of hits from a biochemical screen in a more complex system is still a major challenge but required for further drug development. The discovery of mutations that confer resistance is recognized as the gold standard proof for target engagement. Exploiting the error prone non-homologous end joining after CRISPR-induced double strand breaks, we have developed a high-density tiling CRISPR genetic screen to rapidly deconvolute the target protein and binding site of small-molecule inhibitors based on resistance mutations. The CRISPR guides directly annotate the resistance mutations avoiding the need for whole transcriptome sequencing.

17:15 An Organotypic Slices-based Platform for the Screening of Potential Anti-epileptic Targets Speaker to be AnnouncedOrganotypic slice cultures have become a powerful tool to study brain disorders, since they maintain the cytoarchitecture of the original tissue and reproduce the multicellular brain environment. Entorhinal cortex-hippocampus organotypic slices gradually deprived of serum mimic the epileptic-like activity, as well as the inflammatory events associated with in vivo epilepsy. This system is a new tool to explore the interplay between neuroinflammation and epilepsy, and allows to interfere pharmacologically with inflammatory pathways, such as the NLRP3 inflammasome signalling, prompting the screening of potential targets for antiepileptic drugs.

17:45 Concurrent Toxicity and Efficacy Evaluations of Lead Compounds Utilizing Multi-organ Functional Human-on-a-chip SystemsJames J. Hickman, PhD, Founding Director, NanoScience Technology Center and Professor, Nanoscience Technology, Chemistry, Biomolecular Science, Material Science and Electrical Engineering, University of Central FloridaPhenotypic screening systems for lead optimization have the advantage of providing useful information without a known target. Human-on-chip systems can potentially establish a therapeutic index before evaluation in animal models or clinical trials and also gives the possibility of target identification. Examples of multi-organ systems being developed for cancer and other diseases and conditions as well as the results of six Workshops held at NIH for validation and qualification will be presented.


19:15 Close of Day





Cover

Short Courses






3D Cellular Models













EMERGING CHEMICAL BIOLOGY AND CHEMOGENOMIC SCREENING PLATFORMS

8:55 Chairperson’s RemarksPaul Brennan, PhD, Associate Professor, Medicinal Chemistry, University of Oxford; Principal Investigator, Target Discovery Institute, Structural Genomics Consortium

9:00 KEYNOTE PRESENTATION: Chemical Probes in Target DiscoveryPaul Brennan, PhD, Associate Professor, Medicinal Chemistry, University of Oxford; Principal Investigator, Target Discovery Institute, Structural Genomics ConsortiumChemical probes are selective small molecule inhibitors that can be used in cellular assays to induce a phenotype and link it to a small set of protein targets. Chemical probes have been developed for many bromodomains, the principal epigenetic readers of histone lysine acetylation, and been used to decipher the biology of bromodomains in cancer and inflammation. We are currently developing chemical probes for new protein families.


10:45 Large-Scale Chemogenomics Data: An Enabler for Early Drug DiscoveryFlorian Nigsch, PhD, Chemical Biology and Therapeutics Informatics, Novartis Institutes for BioMedical ResearchThis talk will showcase the impact of the integration of large-scale chemogenomics data on a range of activities in early drug discovery. Topics covered will include pre- and post-screening activities, tool compound discovery, chemoproteomics, as well as applications that link compounds and their transcriptional profiles.

11:15 Chemo-Genomic Screening in AML: A New Approach to Identify Therapeutic Strategies in CancerAnne Marinier, PhD, Principal Investigator and Director of Medicinal Chemistry, IRIC and Associate Professor, Department of Chemistry, Université de MontréalCapitalizing on new leukemia stem cell culture conditions, we developed a chemo-genomic screening approach using genetically and clinically characterized acute myeloid leukemia (AML) specimens and a structurally diverse compound collection. Clustering of hits demonstrating similar specimen inhibition patterns generated CCCs (Compound Correlation Clusters) which reveal sensitized target pathways essential to tumor survival. The CCCs therapeutic relevance will be exemplified by the identification of a novel target for poor prognosis AML.

11:45 A High-Throughput Imaging-Genetic Screen Identifies MEK-PI3K Modulation for TNBCArvind Rao, PhD, Associate Professor, Department of Computational Medicine and Bioinformatics, University of MichiganAs combination therapies enter mainstream clinical oncology, there is now a need for infrastructure to integrate multiple modalities of data to prioritize drug combinations rationally. In this vein, we examine a scenario using machine learning methods to prioritize drug combinations selected based on phenotypic screening via RNAi, coupled with known genetic vulnerabilities in Triple Negative Breast Cancer cells. Such a strategy leverages imaging and genetic information to prioritize the MEKi+PI3Ki combination as a possible regimen.



All Access PricingIncludes access to 2 Conferences, 1 Symposia and 2 Short Courses

Alumni – save 20%

Present a Poster – save €45

Discounted Pricing for Students – pricing starts at €190

Register 3 – 4th is free

Group Discounts are Available! Special rates are available for multiple attendees from the same organization. For more information on group discounts contact Christopher Cardarelli, +1-781-247-1817

WAYSSAVE

to

*Alumni, DSEC Membership, Twitter, LinkedIN, Facebook or any other promotional discounts cannot be combined. Discounts not applicable on Event Short Courses.


mailto:[email protected]


Inaugural

CNS Models and Translational StrategiesTransforming the Discovery and Development of Therapies in Neuroscience

29-30 NOVEMBER 2018



Cover

Short Courses






3D Cellular Models










Despite CNS drugs having seen high attrition rates in recent years, the field of neuroscience is experiencing a substantial renaissance. An improved understanding of CNS disease biology, the discovery of novel drug targets and the application of state-of-the-art technologies, are bringing much needed investment back into this blockbuster therapeutic area. Yet there remains much more to be done in terms of developing reliable preclinical models, validating CNS targets and biomarkers, and bridging the translation gap from preclinical discovery to the clinic. Join us for Cambridge Healthtech Institute’s inaugural CNS Models and Translational Strategies conference, where promising preclinical models will be explored and evaluated, where future steps towards more accurate and reliable preclinical trials will be taken.

Recommended All Access Package:27 November: Single-Cell Analysis27 November Dinner Course: SC1: Immunology Basics for Drug Discovery, Part 1: Immune System Overview28-29 November: Optimizing Leads and Predicting Drug Toxicity29-30 November: CNS Models and Translational Strategies29 November Dinner Course: SC4: Immunology Basics for Drug Discovery, Part 2: Immune-Oncology and Autoimmunity


12:30 Registration

BREAKTHROUGHS IN CNS DISCOVERY13:25 Welcome RemarksJoel Hornby, BSc, Conference Director, Cambridge Healthtech Institute

13:30 Chairperson’s Opening RemarksWilliam Z. Potter, MD, PhD, Senior Advisor, National Institute of Mental Health, National Institutes of Health (NIH)

13:35 Principles for Delivering Breakthrough Drug Discovery for CNS DisordersStuart W. Hughes, PhD, Director and Head of Pharmacology, Biological Sciences, Vertex PharmaceuticalsCNS drug discovery presents a set of unique challenges that renders this therapeutic area a particularly tough nut to crack. Whether it be identifying novel validated targets that are grounded in robust human biology, clearly defining the translational value of specific animal models or creating appropriate biomarkers that enable effective development of clinical molecules, delivering success has proven far from easy. In this talk, I will discuss a set of key principles that address all of these pivotal issues.

14:05 Testing the Diseased Brain on the Chip: From Gene Expression to Functional Phenotyping of Patient-Derived Neuronal CulturesDirk Schubert, PhD, Assistant Professor, Group Leader “Cellular Neurophysiology”, Cognitive Neuroscience Department, Donders Institute for Brian, Cognition & Behaviour, Radboud University Medical Clinic Nijmegen

Human induced pluripotent stem cell derived neurons (iNeurons) from control lines as well as from patients can be used to unravel the mechanisms that underlie impaired network function and synaptic communication in patients with neurodevelopmental disorders, such as intellectual disability. Studying neuronal network formation and maturation by investigating molecular, structural and functional parameters revealed robust disease phenotypes that offer the platform for testing pharmacological interventions.

SELECTED POSTER PRESENTATIONS14:35 Characterization of Human Pluripotent Stem Cell derived Neural Progenitor CellsÁgota Apáti, PhD, Senior scientist, Leader of Human Pluripotent Stem Cell Laboratory, Institute of Enzymolgy, Research Center for Natural Sciences- Hungarian Academy of SciencesHuman pluripotent stem cells (hPSC) offer a new perspective to overcome the limitation of existing models. In the present study neural progenitor cells (NPCs), which are committed to produce PROX-1-positive granule cells, were generated from hPSCs. Studying morphology, growth and differentiation capacity, neurite outgrowth and calcium signaling suggested that NPCs differentiated from hPSCs provide a reliable in vitro model system suitable for studying special aspects of neural development and regeneration.

14:50 Pathway Sensor-Based Functional Genomics Screening Identifies Modulators of Neuronal ActivityAlexander Herholt, PhD student, Ludwig-Maximilians University MunichDespite the wealth of functional genomics screens for proliferation and toxicity using RNA interference (RNAi) or CRISPR/Cas9, neuronal signaling has been difficult to address so far. To overcome this limitation, we developed a novel pooled screening assay which combines barcoded activity reporters with pooled genetic perturbation in a dual-expression adeno-associated virus (AAV) library. With this we aim at pathway dissection and target identification in patient-derived cellular models of neuropsychiatric diseases.







Cover

Short Courses






3D Cellular Models











STEM CELL AND iPSC BASED CNS MODELS16:45 Testing Drugs That Modulate Mitochondrial Biogenesis and Function in iPSC Models of Neurodegenerative DiseasesMichela Deleidi, PhD, Helmholtz Young Investigator Group Leader, DZNEWhile mitochondrial dysfunction is emerging as key in neurodegenerative diseases, a central question remains whether mitochondria are actual disease drivers and boosting mitochondrial biogenesis and function ameliorates pathology. We outline how patient-derived induced pluripotent stem cells and genome editing can be used for modelling mitochondrial demise occurring in neurodegenerative conditions such as Parkinson’s and Alzheimer’s disease. We outline progress in screening for compounds that improve energy metabolism and ameliorate neurodegenerative phenotypes.

17:15 Exploiting Human Stem Cells to Recapitulate Pathological Signatures of Human Brain MicroenvironmentCatarina Brito, PhD, Lab Head, Advanced Cell Models Lab – Animal Cell Technology Unit, iBET & ITQB-NOVAWe have been exploiting platforms based on spheroid culture in perfusion stirred tank bioreactors for generation of functional neurospheroids - 3D structures containing neurons, astrocytes and oligodendrocytes, derived from human induced pluripotent stem cells. Recent data on the characterization of the cell microenvironment generated within neurospheroids will be presented. The application of neurospheroids as in vitro models to address molecular defects associated with neurological disorders that affect neural microenvironment homeostasis and as potency assays for drug testing will also be discussed.

17:45 Metabolic Profiling of Human Neural Cells for Disclosing Metabolic Determinants and Cell-Cell InteractionsDaniel Simão, PhD, Senior Research Associate, Animal Cell Technology Unit, Instituto de Biologia Experimental e Tecnologica (iBET)Metabolism plays an important role on cell fate, generating input signals that affect cellular dynamics at multiple levels. Different applications of metabolic characterization tools for neural stem cell-derivatives will be presented, encompassing the interrogation of toxicants’ effects on neuron-astrocyte interactions and determination of cell identity metabolic features. Overall, such strategies contribute for the identification of key metabolites in different cell types, which can have an impact for the design of targeted approaches for stem cell bioprocessing.


19:00 – 21:30 Recommended Dinner Short Course*SC4: Immunology Basics for Drug Discovery, Part 2: Immune-Oncology and Autoimmunity* Separate registration required, see page 3 for details.

FRIDAY 30 NOVEMBER


COMPARING ANIMAL MODELS FOR CNS RESEARCH

8:55 Chairperson’s RemarksRavi Jagasia, PhD, Research Scientist, CNS, Hoffmann-La Roche, Roche Innovation Center Basel

9:00 Nonclinical Models Supporting Orphan Drug Designations in Rare Neurodegenerative ConditionsDinah Duarte, PhD, Assistant Professor, Lisbon University; Senior Assessor, INFARMED; PT Member, Committee for Orphan Medicinal Products, European Medicines Agency (EMA)Many disease-specific animal models have been used to test emergent medicines in neurology. There is a body of evidence, however, that there is a substantial difficulty in choosing/accessing an optimal model or choosing measurements which would be truly informative of the product’s efficacy. We intend to present a critical revision of preclinical models that may be used to support orphan drug designations in rare neurodegenerative conditions, which are validated for each condition and to evaluate assays pertinent to the core features of selected conditions or otherwise relevant from the clinical standpoint.

9:30 Reports Given by Moderators from Thursday Afternoon Breakout DiscussionsStuart W. Hughes, PhD, Director and Head of Pharmacology, Biological Sciences, Vertex Pharmaceuticals William Z. Potter, MD, PhD, Senior Advisor, National Institute of Mental Health, National Institutes of Health (NIH)


TRANSLATIONAL CNS STRATEGIES10:45 Translating Neuroscience into Treatments: De-Risking through PartnershipsWilliam Z. Potter, MD, PhD, Senior Advisor, National Institute of Mental Health, National Institutes of Health (NIH)Translating the findings of neuroscience since the 1980’s into novel treatments for brain disorders has proven much more challenging than anticipated. The definitive methods required to be sure that one is validating or rejecting hypotheses on the potential of novel molecular interventions are sparse and unlikely to be developed within any single entity with the notable exception of PET ligands for orthosteric antagonists. The field is therefore exploring multiple public/private partnerships to develop and share the tools for ruling in or out the utility of novel intervention. A still-to-be-implemented possibility would be a true pre-competitive effort to de-risk a particular mechanism through a shared validation effort followed by some means of distributing the commercial rewards of finding the best molecule to affect the validated target.

11:15 From Gut-Brain Explorations to Effective Innovative Therapies in Parkinson DiseasePatrice Garnier, PhD, CEO, AmabioticsDue to millions of years of coevolution, complex metabolic interactions exist between human and its gut microbiota. Not surprisingly, the number of reports associating dysbiosis and systemic diseases increased drastically over the past years. Amabiotics is a biopharmaceutical company that develops innovative diagnostics and microbiome-derived medicines to cure neurodegenerative diseases. Its lead compound, AMA-101 is targeted against Parkinson’s disease.





Cover

Short Courses






3D Cellular Models











11:45 Human Pluripotent Stem Cells in ASD DiscoveryRavi Jagasia, PhD, Research Scientist, CNS, Hoffmann-La Roche, Roche Innovation Center BaselThe study of neurodevelopmental diseases, including autism spectrum disorders (ASD), and the development of effective treatments have been limited by a lack of appropriate models. Rodent models cannot model the complexity of the human genome and brain development in physiology and disease. To this end, human induced pluripotent stem cells (iPSC) represent a potentially limitless supply of patient-specific cells for the study of ASD.


NOVEL CNS STRATEGIES13:40 Chairperson’s RemarksStuart W. Hughes, PhD, Director and Head of Pharmacology, Biological Sciences, Vertex Pharmaceuticals

13:45 Dissecting Pathologic Molecular Signatures in Neurodegenerative Diseases through Chemical Chaperomics – From Mechanisms to Diagnostics and TreatmentGabriela Chiosis, PhD, Professor, Member, Attending, Chemical Biology and Medicine, Memorial Sloan Kettering Cancer CenterI aim to discuss chemical chaperomics, a functional proteomics platform applicable for systematic proteomewide investigations of molecular alterations in Alzheimer’s disease and other neurodegenerative diseases. The method provides large-scale unbiased information on global protein-protein interactions and pathologic protein function changes in response to genetic and environmental factors. Implementation of this method to the analysis of patient-derived specimens may provide important information that is unavailable through, but complementary, to other ‘omics’ methods.

14:15 Antibodies for Brain Disorders Using the Brain Shuttle Blood-Brain Barrier Transport TechnologyPer-Ola Freskgård, PhD, Vice Director & Expert Scientist, Neuroscience, Roche Pharma Research & Early DevelopmentThis talk will briefly describe the status of the brain delivery field of biologics to the brain by highlighting recent advancements. In particular, the Brain Shuttle technology will be described, which is designed to be engineered into a standard therapeutic antibody and other types of biologics for successful BBB transport. Efficiency and safety aspects will be addressed illustrated with recent experimental data.

14:45 Progress in Neuroengineering for Brain Repair: From in vitro to in vivo Studies and BeyondMichela Chiappalone, PhD, Researcher (Team Leader), Rehab Technologies, Italian Institute of Technology (IIT)In recent years, biomedical devices have been developed to target different neurological disorders. To reach useful therapeutic results, these tools need a multidisciplinary approach and a continuous dialogue between neuroscience and engineering, a field named Neuroengineering. In this talk, I will highlight the importance of developing novel neurotechnologies for brain repair (exploiting both in vitro and in vivo animal models) and present the major challenges expected for the next years.

15:15 Extended Q&A on Novel CNS Strategies


Maximize your experience on-site at World Preclinical Congress Europe 2018!

CHI’s 1-on-1 networking service offers you the opportunity to set up meetings with selected attendees before, during and after this conference, allowing you to connect to the key people you want to meet. This online system was designed with your privacy in mind and is available only to registered session attendees of this event. Registered conference attendees will receive more information on accessing the networking service in the weeks leading up to the event.

1-ON-1 NETWORKING





Inaugural

NASH and Fibrosis: Translational Research and StrategiesDrug Development for Diseases of the Fatty Liver and Fibrosis

28-29 NOVEMBER 2018



Cover

Short Courses






3D Cellular Models










Non-alcoholic Steatohepatitis (NASH) is the result of a fatty liver that starts to undergo fibrosis, whose scarring can eventually lead to a liver that is non-functional. The increasing global incidence of NASH may be linked to the concomitant rise in diabetes, obesity and other metabolic disorders all over the world. No pharmaceutical treatment yet exists for NASH, but it is an area of active research and industry focus, with several treatments in late-stage clinical trials. However, many translational challenges remain, such as non-invasive ways to measure disease progression and response to treatment and best ways to model the disease outside of the patient. Join fellow drug discovery researchers working in the area of liver disease and fibrosis to stay abreast of clinical and preclinical advances in the field and share insights on translational tools and approaches for spurring drug development progress.

Recommended All Access Package:27 November: Organ-on-a-Chip and MicroPhysiological Systems27 November Dinner Course: SC1: Immunology Basics for Drug Discovery, Part 1: Immune System Overview28-29 November: NASH and Fibrosis: Translational Research and Strategies29-30 November: Induced Pluripotent Stem Cells29 November Dinner Course: SC4: Immunology Basics for Drug Discovery, Part 2: Immune-Oncology and Autoimmunity



COMPOUNDS IN DEVELOPMENT FOR NASH8:50 Welcome RemarksAnjani Shah, PhD, Senior Conference Director, Cambridge Healthtech Institute

8:55 Chairperson’s RemarksRebecca Taub, MD, CMO & Executive Vice President, R&D, Madrigal Pharmaceuticals

9:00 Development of Elafibranor -- a Dual PPARα/δ Agonist for the Treatment of NASHRobert Walczak, PhD, Executive Vice President, Head of Research, GenfitElafibranor is a first-in-class PPARα/δ agonist which has demonstrated in a Phase IIb study NASH resolution without the worsening of fibrosis while also improving cardio-metabolic risk. Furthermore, NASH resolution correlated with fibrosis improvement. Elafibranor is safe, tolerable and is now being investigated in Phase III. Additionally, GENFIT is developing a blood-based in vitro diagnostic to identify NASH patients who are at risk of disease progression and should be considered for therapeutic intervention - a key unmet clinical need.

Sponsored by9:30 Metabolomic Profiling to Identify Molecular Determinants of Liver DiseaseNicolas Schauer, PhD, Managing Director, Metabolon, Inc.A diverse set of disease drivers including genetics, environmental cues, microbiota metabolism and lifestyle influences come together resulting in an uncertain natural history of NAFLD/NASH. Metabolomics provides a comprehensive picture of the metabolome and maps metabolites to their key biochemical pathways providing a holistic assessment of complex diseases.


COMPOUNDS IN DEVELOPMENT FOR NASH (CONT.)10:45 Thyroid Hormone Receptor AgonistsRebecca Taub, MD, CMO & Executive Vice President, R&D, Madrigal PharmaceuticalsI will present topline public data from our latest clinical study on MGL-3196, a β-selective thyroid hormone receptor (THR) agonist. MGL-3196 is an orally administered, small-molecule, liver-directed compound that is currently in Phase II development for NASH. The data show highly significant reduction of liver fat and biomarkers of inflammation and fibrosis at 12 weeks in a 36 week serial liver biopsy study.

11:15 KEYNOTE PRESENTATION: Targeting GLP-1 for NASHKarin Conde-Knape, PhD, Corporate Vice President, Cardiovascular and Liver Disease Research, Novo NordiskGLP1 receptor agonists have been successfully positioned for the treatment of diabetes and obesity. It has been documented that weight loss either by dietary or surgical intervention leads to improvement in NASH and fibrosis. Initial clinical data suggests a beneficial effect of GLP1 receptor agonists in NASH clinical trials. An overview of GLP1 receptor agonism in the treatment of NASH and future directions will be provided.


TRANSLATIONAL-STAGE RESEARCH IN NASH13:45 Chairperson’s RemarksDiane Shevell, PhD, Director, Clinical Biomarkers and Innovative Medicines Development, Bristol-Myers Squibb

13:50 Animal Models of NASH in Preclinical Drug Development





Cover

Short Courses






3D Cellular Models











Iwona Ksiazek, PhD, Senior Investigator I, Chemical Biology & Therapeutics, Novartis Institutes for Biomedical ResearchDespite the tremendous progress in development and characterization of animal models of NAFLD/NASH made over the last years, we still lack robust and appropriately validated preclinical models with proven clinical translatability. Advantages and limitations of selected mouse NASH models used to test pharmacological agents will be discussed and a newly developed diet-induced obesity model of NASH with fibrosis will be presented, covering the diet, systemic metabolic and inflammatory milieu, as well as the histological spectrum of human NASH disease and its application in drug discovery, including validation with drugs currently in clinical development for NASH

14:20 FXR Agonists and LXR Inverse Agonists for the Treatment of NASHClaus Kremoser, PhD, CEO, Phenex



16:45 Report-back from Breakout Discussions

17:15 Navigating Liver-Derived Omics Data for Translational ResearchFlorian Nigsch, PhD, Senior Investigator I, Chemical Biology and Therapeutics, Data Science,Novartis Institutes for BioMedical Resesarch, BaselTranslational research is of paramount importance for drug discovery, and computational techniques can play a major role. This talk will focus on common challenges of computational translational liver research, and then provide some insights with specific examples based on omics datasets of disease models, in vitro and in vivo, including single cell analyses of human liver tissue.

17:45 MTBL0036, a Promising, New Anti-NASH and Antifibrotic CandidateGabriel Baverel, PhD, President, Founder, CSO, Metabolys, Inc.MTBL0036 is a small molecule, orally active with favorable PK characteristics, and safe. In the STAM mouse model of NASH, it greatly diminished the NAFLD Activity Score by drastically reducing inflammation and ballooning, the major drivers of fibrosis. In mice fed a choline deficient amino acid defined high fat diet, it greatly ameliorated liver fibrosis. Unlike that of most anti-NASH candidates in development, its molecular target is not nuclear.


19:15 Close of Day



NASH AND FIBROSIS TRANSLATIONAL TOOLS8:55 Chairperson’s RemarksIwona Ksiazek, PhD, Senior Investigator I, Chemical Biology & Therapeutics, Novartis Institutes for Biomedical Research

9:00 KEYNOTE PRESENTATION: Biomarkers to Assess the Impact of Therapeutics on Patients with Liver Fibrosis Diane Shevell, PhD, Director, Clinical Biomarkers and Innovative Medicines Development, Bristol-Myers SquibbNon-alcoholic steatohepatitis (NASH), the most advanced form of non-alcoholic fatty liver disease (NAFLD), is characterized by steatosis with inflammation and liver cell injury, which can lead to liver fibrosis. Non-invasive, accurate biomarkers are needed to identify patients at high risk for NASH and to monitor disease progression. The potential use of non-invasive biomarkers to characterize patients with NASH and their response to an investigational therapy will be presented.

9:30 Identification of NAFLD in Primary Care: Can Algorithms and Transient Elastography (TE) Predict Fibrosis?Helena Cortez-Pinto, MD, PhD, Professor, Department of Gastroenterology, Faculty of Medicine of LisbonNAFLD is extremely frequent in primary care. However it is generally unrecognized or devalued by general practitioners. Although screening in the general population is not recommended, the rules of referral to specialists and the population to be screened needs better definition. Definition of these groups, what are the best algorithms and role of TE to predict fibrosis severity will be presented.


NASH AND FIBROSIS TRANSLATIONAL TOOLS (CONT.)10:45 IL-1 beta Small Molecule Inhibitors for the Treatment of NASHJuan J. Perez, PhD, Professor, Deptartment of Chemical Engineering, Universitat Politecnica de Catalunya-BarcelonaTech

11:15 Modelling of NAFLD/NASH with Patient-Derived iPS CellsJames Adjaye, PhD, Professor,Director, Institute for Stem Cell Research and Regenerative Medicine, Heidrich Heine University, Dusseldorf, GermanySteatosis leading to NAFLD and NASH should be considered as a multifactorial metabolic disease. Studies based on rodents, patient liver-biopsies and serum have provided useful insights into the etiology of steatosis. Though useful, a better understanding of disease mechanisms, biomarker discovery and drug development necessitates the use of hepatocyte-like cells differentiated from patient derived induced pluripotent stem cells. My talk will focus on genes and associated pathways implicated in disease progression.

11:45 CANCELLED: Novel Serum and Imaging Markers for Advanced Fibrogenesis and FibrolysisDetlef Schuppan, MD, PhD, Director, Institute of Translational Immunology, University of Mainz





Inaugural

Induced Pluripotent Stem Cells iPSC and Stem Cell Models for Preclinical Screening

29-30 NOVEMBER 2018



Cover

Short Courses






3D Cellular Models










The discovery and development of techniques for generating and manipulating induced pluripotent stem cells (iPSCs) is viewed by many as one of the crowning achievements of modern day science. However promising, their application in the field of regenerative medicine is yet to be fully realised. The growing use of iPSCs for disease modelling, safety and efficacy screening in preclinical drug discovery may yet be where they have the biggest impact. Cambridge Healthtech Institute’s inaugural conference on Induced Pluripotent Stem Cells covers some of the diverse applications of these cells for disease modelling, target discovery, lead optimization, functional screening, drug safety screening and more.




USE OF STEM CELLS FOR DRUG SAFETY ASSESSMENTS8:25 Chairperson’s RemarksChristopher Goldring, PhD, Senior Lecturer, Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool

8:30 Importance of Phenotyping Your Model to Know What Purpose It Is Fit ForChristopher Goldring, PhD, Senior Lecturer, Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of LiverpoolIt is estimated that 38% and 51% of compounds showing liver injury in man do not show similar effects in animals. The work of the IMI MIP-DILI and TransQST consortia shows how a roadmap is being developed based for the integration of established and emerging test systems and illustrates the increasing complexity of models from 2D to multi-cell 3D systems that are used in a logical fashion to assess DILI liabilities of new drugs before they are given to man.

9:00 Bioengineering Human Pluripotent Stem Cell Derived 3D Models for Drug Toxicity and Disease ModelingPaula M. Alves, PhD, Unit Director, Cell Bioprocesses Laboratory, Instituto de Biologia Experimental e Tecnologica (iBET)The development and validation of human in vitro models with physiological relevance, robustness, reproducibility and scalability are still a need in toxicology.

Our strategy combines human stem cells, 3D culture strategies and computer-controlled bioreactors in perfusion operation modes. Results concerning the establishment and refinement of culture systems for efficient stem cell differentiation and maturation into cardiac, neural and hepatic cells, as well as their applicability for long-term toxicity testing will be presented and discussed.

Sponsored by9:30 Rethinking the Translational – The use of Highly Predictive hiPSC-Derived Models in Pre-clinical Drug DevelopmentAlexandre Fouassier, Business Development & Sales, Southern Europe, NcardiaCurrent drug development strategies are failing to increase the number of drugs reaching the market. One reason for low success rates is the lack of predictive models. Join our talk to learn how to implement a predictive and translational in vitro disease model, and assays for efficacy screening at any throughput.

10:00 Coffee Break in the Exhibit Hall

10:45 Exploring the Relationship between Myofilament Calcium and Force Production in the Single iPS-CardiomyocytesMatthew J. Daniels, MA, PhD, MRCP, Wellcome Trust Intermediate Clinical Fellow, Principal Investigator, Division of Cardiovascular Medicine, and BHF Oxbridge Centre of Regenerative Medicine, Oxford UniversityThe in vitro survival of iPS-CMs should aid cardiotoxicity studies of contractility. As contraction depends on depolarisation, both parameters should be measured in these assays. We find that all classes of chemical dye (voltage, calcium & sodium) impair contractility, and when used in combination with drugs known to act on the myofilament produce confusing composite results making them unreliable for this purpose. We describe how we have overcome this problem.

11:15 Phenotypic Analysis for Cardiotoxicity Evaluation on hiPSCAnthony Perrier, PhD, Study Director, In vitro Toxicology, Biologie ServierTo improve the early prediction of cardiac toxicity, we developed in vitro tests using High Content Analysis using human iPSC cardiomyocytes. The readouts were qualified using Receiver Operating Characteristic curves and a ranking algorithm was developed to obtain an overall multiparametric cardiotoxicity evaluation for each compound. This cardiotoxicity phenotypic analysis and ensuing improvements will be used for early safety evaluation in the drug development process at Servier.





Cover

Short Courses






3D Cellular Models










Induced Pluripotent Stem CellsiPSC and Stem Cell Models for Preclinical Screening

11:45 Evaluating Cardiovascular Liability and Genetic Disease with hiPSC-CardiomyocytesChris Denning, PhD, Professor and Head, Department of Stem Cell Biology, University of NottinghamWe will review the results from a public-private partnership (NC3Rs-GSK), termed the “CRACK-IT InPulse Challenge” and the software developed to facilitate analysis of cardiac contractility. This sought to evaluate hiPSC-cardiomyocytes in 2D and 3D formats in the blinded evaluation of 28 drugs that were associated with positive or negative inotropy in heart tissue, or no effect. Finally, we will show data on the coupling of hiPSC-CMs and Cas9/CRISPR-mediated gene editing to model hypertrophic cardiomyopathy.


iPSC-BASED 3D MODELS - I13:25 Welcome RemarksJoel Hornby, BSc, Conference Director, Cambridge Healthtech Institute

13:30 Chairperson’s Opening RemarksHansjoerg Keller, PhD, Senior Investigator I, Musculoskeletal, Novartis Institutes for BioMedical Research

13:35 Human Heart-in-a-Jar from iPSC for Disease Modelling and Drug ScreeningRonald A. Li, PhD, Director and Professor, Ming Wai Lau Center for Reparative Medicine, Karolinska InstitutetTraditional drug development is an inefficient and expensive process with unacceptably high failure rates. Major species-specific differences limit the ability of animal models to predict human cardiotoxicity, the dominant reason for attrition. Here, I will present various human ESC/iPSC-derived engineered heart constructs that our group has designed specifically for studying electrophysiology and contractility, including our latest fluid-ejecting “human heart-in-a-jar” that uniquely enables the measurements of clinically complex parameters such as cardiac output, ejection fraction, PV loops.

14:05 An in vitro 3D Kidney Model – Generation and Application in a Pharmaceutical SettingAnna Jonebring, MSc, Senior Scientist, Translational Genomics, Discovery Sciences IMED Biotech Unit, AstraZenecaA disease like chronic kidney disease (CKD), affecting approximately 10% of the population, is one of the areas where there is a great unmet need for innovative pharmacological therapies. Within AstraZeneca we are working with human iPSCs derived 3D kidney models in a platform approach to drive the TI/TV activities as well as developing a highly efficient model for safety/toxicology applications. Combining the 3D model with CRISPR/Cas9, Next-Generation Sequencing (NGS), functional testing and advanced imaging techniques, our 3D kidney platform is evolving and becoming an essential part in our drug discovery process.

Sponsored by14:35 A Novel High-Throughput Multi-Parametric Drug Screening Method for 3D Tumor Spheroids Using Celigo Image CytometerSuzanne Riches, PhD, Technology Research & Development, Manager, Nexcelom

Bioscience LLCThere is an increase in utilizing 3D spheroid for drug screening. We demonstrated a cancer drug scoring method using multi-parametric analysis to rank the anti-cancer effects of drugs on tumor spheroids. The assays conducted were growth inhibition, perimeter cell-death, and viability. Drugs can be screened to identify potential drug candidates.

15:05 Interactive Breakout Discussion GroupsThis session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas and active networking. Details on the topics and moderators are available on the conference website


STEM CELL AND iPSC-BASED CNS MODELS16:45 Testing Drugs That Modulate Mitochondrial Biogenesis and Function in iPSC Models of Neurodegenerative DiseasesMichela Deleidi, PhD, Helmholtz Young Investigator Group Leader, DZNEWhile mitochondrial dysfunction is emerging as key in neurodegenerative diseases, a central question remains whether mitochondria are actual disease drivers and boosting mitochondrial biogenesis and function ameliorates pathology. We outline how patient-derived induced pluripotent stem cells and genome editing can be used for modelling mitochondrial demise occurring in neurodegenerative conditions such as Parkinson’s and Alzheimer’s disease. We outline progress in screening for compounds that improve energy metabolism and ameliorate neurodegenerative phenotypes.

17:15 Exploiting Human Stem Cells to Recapitulate Pathological Signatures of Human Brain MicroenvironmentCatarina Brito, PhD, Lab Head, Advanced Cell Models Lab – Animal Cell Technology Unit, iBET & ITQB-NOVAWe have been exploiting platforms based on spheroid culture in perfusion stirred tank bioreactors for generation of functional neurospheroids - 3D structures containing neurons, astrocytes and oligodendrocytes, derived from human induced pluripotent stem cells. Recent data on the characterization of the cell microenvironment generated within neurospheroids will be presented. The application of neurospheroids as in vitro models to address molecular defects associated with neurological disorders that affect neural microenvironment homeostasis and as potency assays for drug testing will also be discussed.

17:45 Metabolic Profiling of Human Neural Cells for Disclosing Metabolic Determinants and Cell-Cell InteractionsDaniel Simão, PhD, Senior Research Associate, Animal Cell Technology Unit, Instituto de Biologia Experimental e Tecnologica (iBET)Metabolism plays an important role on cell fate, generating input signals that affect cellular dynamics at multiple levels. Different applications of metabolic characterization tools for neural stem cell-derivatives will be presented, encompassing the interrogation of toxicants’ effects on neuron-astrocyte interactions and determination of cell identity metabolic features. Overall, such strategies contribute for the identification of key metabolites in different cell types, which can have an impact for the design of targeted approaches for stem cell bioprocessing.





Cover

Short Courses






3D Cellular Models










Induced Pluripotent Stem CellsiPSC and Stem Cell Models for Preclinical Screening



FRIDAY 30 NOVEMBER


iPSC-BASED 3D MODELS - II8:55 Chairperson’s RemarksMarine Kraus, PhD, Specialist, Group Leader, Stem Cell, Nestle Institute of Health Sciences SA

9:00 Organoids: A Next-Generation in vitro Model That Captures Clinical ResponseLyle Armstrong, PhD, Professor of Cellular Reprogramming & CSO, Newcells Biotech Ltd., Institute of Genetic Medicine, Newcastle UniversityToxicity testing based upon animal models or transformed cell lines is not always an accurate representation of the response of human tissues and organs to xenobiotic substances. The development of human pluripotent stem cells, which are capable of generating many of the cell types found in the adult body may be an effective solution to address this problem therefore this lecture will attempt to present not only the background of what pluripotent stem cells are and how they are made but also how we can use them to produce versatile new toxicity assays for use in pharmaceutical development.

9:30 In vitro Generation of Functionally Mature Beta-Cells from Adult Human iPSCsMarine Kraus, PhD, Specialist, Group Leader, Stem Cell, Nestle Institute of Health Sciences SAIslet transplantation has demonstrated that replacement of the beta-cell mass in diabetic patients is able to restore endogenous glycaemic control. Stem-cell therapies hold great promise for generating a replenishable supply of insulin producing beta-cells for transplantation. In the present studies, we report the in vitro generation of functionally mature beta-cells from human iPSCs. These newly generated beta-cells display mature features and exhibit glucose regulated insulin secretion, displaying the first and second insulin release phases characteristic of human islets.


STEM CELL-BASED 3D MODELS10:45 Novel 3D Hepatic in vitro Systems for Studies of Chronic Drug Toxicity and Liver DiseaseMagnus Ingelman-Sundberg, PhD, BSc.Med, Professor, Department of Physiology and Pharmacology, Karolinska InstitutetUsing a model of 3D PHH spheroids we observed that drug metabolism was preserved for several weeks of cultivation and that transcriptomic, proteomic and metabolomics analyses revealed similar phenotype as in freshly isolated hepatocytes. In addition, using these 3D spheroid systems we have been able to mimic different liver disease like NAFLD, NASH and fibrosis and found the system suitable for evaluation of mechanisms behind and for identification of drug candidates. In the lecture recent results describing the properties and usefulness of the system will be presented.

11:15 Modeling Kidney Development and Disease through 3D OrganoidsNuria Montserrat, PhD, Group Leader, Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC)Our aim is to facilitate basic knowledge on kidney engineering providing novel approaches facilitating renal maturation and function. We have generated kidney organoids from human pluripotent stem cells. In parallel, we have developed biomimetic inks for bioprinting 3D kidney structures. Lastly, using a novel transplantation method we have further maturated and vascularized kidney organoids. We provide innovative solutions when translating these technologies into the clinical setting.

11:45 Organoids: A Next-Generation in vitro Model That Captures Clinical ResponseRobert Vries, PhD, Managing Director, Stichting Hubrecht Organoid TechnologiesThe laboratory of Hans Clevers, the founder of HUB, previously discovered the identity of adult stem cells in many human tissues such as intestine and liver (Barker et al., Nature 2007; Huch et al., Nature 2013). More recently, we were able to demonstrate that the in vitro response of organoids directly correlates with the clinical outcome of the patient from which the organoid was derived (Dekkers et al., Sci Trans Med 2016; Sachs et al., Cell 2018). In addition, we have now developed a novel system that allows the co-culture of organoids with immune cells to study the effect of immune modulating drugs.


PRESENT A POSTER AND SAVE €45!Cambridge Healthtech Institute encourages attendees to gain further exposure by presenting their work in the poster sessions. To secure a poster board and inclusion in the conference materials, your abstract must be submitted, approved and your registration paid in full by 19 October 2018.Reasons you should present your research poster at this conference:• Your research will be seen by our international delegation,

representing leaders from top pharmaceutical, biotech, academic and government institutions

• Receive €45 off your registration• Your poster abstract will be published in our conference materials




Cover

Short Courses






3D Cellular Models










How to Register: [email protected] • P: 781.972.5400 or Toll-free in the U.S. 888.999.6288

Please use keycode WPE F

when registering!

Pricing and Registration InformationCONFERENCE PRICING

ALL ACCESS PRICING (Includes access to 2 Conferences, Academic, Government, 1 Symposia and 2 Short Courses) Commercial Hospital-affiliatedAdvance Registration Discount until 26 October 2018 €2749 €1499Registrations after 26 October 2018, and on-site €2899 €1599

PREMIUM CONFERENCE PRICING (Includes access to 2 Conferences)Advance Registration Discount until 26 October 2018 €1849 €879Registrations after 26 October 2018, and on-site €1999 €929

SINGLE CONFERENCE PRICING (Includes access to 1 Conference)Advance Registration Discount until 26 October 2018 €1299 €599Registrations after 26 October 2018, and on-site €1499 €629

SYMPOSIA PRICING

One Symposia €999 €599

Tuesday 27 November (Symposia) Wed. 28 Nov. - Thurs. 29 Nov. Morning Thurs. 29 Nov. Afternoon - Fri. 30 Nov.S1: Organ-on-a-Chip and MicroPhysiological Systems

C1: Target Identification & Validation Strategies C5: 3D Cellular Models

S2: Single-Cell Analysis C2: Preclinical Models for Cancer Immunotherapy and Combinations

C6: Translational Biomarkers in Immuno-Oncology

S3: Artificial Intelligence & Machine Learning for Drug Discovery

C3: Optimizing Leads and Predicting Drug Toxicity

C7: CNS Models and Translational Strategies

C4: NASH and Fibrosis: Translational Research and Strategies

C8: Induced Pluripotent Stem Cells

SHORT COURSE PRICINGOne short course €625 €375Two short courses €895 €625

27 November, 18:00-20:30 29 November, 19:30-21:00SC1: Immunology Basics for Drug Discovery, Part 1: Immune System Overview

SC4: Immunology Basics for Drug Discovery, Part 2: Immune-Oncology and Autoimmunity

SC2: Understanding Key Concepts in Drug Metabolism and Drug Transport SC5: Humanized Mouse Models: Technology and Applications in Preclinical Assessment of Cancer Immunotherapy

SC3: The Origins, Optimization and Application of Organ-on-a-Chip Systems

CONFERENCE DISCOUNTS

Poster Submission - Discount (€45 Off): Poster abstracts are due by 19 October 2018. Once your registration has been fully processed, we will send an email containing a unique link allowing you to submit your poster abstract. If you do not receive your link within 5 business days, please contact

ADDITIONAL REGISTRATION DETAILSEach registration includes all selected conference sessions, posters and exhibits, food functions, and access to the conference proceedings link.Handicapped Equal Access: In accordance with the ADA, Cambridge Healthtech Institute is pleased to arrange special accommodations for attendees with special needs. All requests for such assistance must be submitted in writing to CHI at least 30 days prior to the start of the meeting.To view our Substitutions/Cancellations Policy, go to healthtech.com/regdetailsVideo and or audio recording of any kind is prohibited onsite at all CHI events.

[email protected]. *CHI reserves the right to publish your poster title and abstract in various marketing materials and products.

REGISTER 3 - 4th IS FREE: Individuals must register for the same conference or conference combination and submit completed registration form together for discount to apply.

Alumni Discount: Cambridge Healthtech Institute (CHI) appreciates your past par-ticipation at World Preclinical Congress. As a result of the great loyalty you have shown us, we are pleased to extend to you the exclusive opportunity to save an additional 20% off the registration rate.

Group Discounts: Discounts are avail-able for multiple attendees from the same organization. For more informa-tion on group rates contact Christopher Cardarelli at [email protected], +1-781-247-1817.

If you are unable to attend but would like to purchase the World Preclinical Congress Europe 2018 CD for €600 (plus shipping), please visit WorldPreclinicalEurope.com. Massachusetts delivery will include sales tax.



mailto:reg%40healthtech.com?subject=

http://www.healthtech.com/regdetails

mailto:jring%40healthtech.com?subject=

mailto:ccardarelli%40healthtech.com?subject=

mailto:ccardarelli%40healthtech.com?subject=

EUROPE Technologies EUROPE 27 - 30 November 2018 · Comprehensive sponsorship packages allow you to...

Documents

Transcript of EUROPE Technologies EUROPE 27 - 30 November 2018 · Comprehensive sponsorship packages allow you to...