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Functional Analysis & Screening Technologies

C O N G R E S S

C A M B R I D G E H E A L T H T E C H I N S T I T U T E ’ S S E C O N D A N N U A L

NOVEMBER 17-19, 2014 • HYATT BOSTON HARBOR • BOSTON, MA

NOVEMBER 17-18 NOVEMBER 18-19

Join 250+ R&D teams for practical discussions, solutions and case studies for refining early-stage

drug discovery methods!

Phenotypic Drug Discovery - Part I

Phenotypic Drug Discovery - Part II

Engineering Functional 3D Models

Screening & Functional Analysis of 3D Models

Organotypic Culture Models for Toxicology

Physiologically-Relevant Cellular Tumor Models for Drug Discovery

REGISTER BYAUGUST 22 & SAVE UP TO

$400!

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Sunday, Nov. 16 Monday, Nov. 17 Tuesday, Nov. 18 Wednesday, Nov. 19

AM Phenotypic Drug Discovery - Part I

PM Phenotypic Drug Discovery - Part II

AM Engineering Functional 3D Models

PM Screening & Functional Analysis of 3D Models

AM Organotypic Culture Models for Toxicology

PM

Dinner Short Courses*

CONGRESS AT-A-GLANCE

ABOUT THE CONGRESSCambridge Healthtech Institute (CHI) is proud to release the final agenda for the 2nd Annual FAST: Functional Analysis & Screening Technologies Congress to be held on November 17-19, 2014 in Boston, MA. Join our community of 250+ engineers, biologists, screening managers and pharmacologists dedicated to improving in vitro cell models and phenotypic screening to advance drug discovery and development at six conferences, interactive short courses, and in our exhibit/poster hall.

*Separate registration required

KEYNOTE SPEAKERS

Physiologically-Relevant Cellular Tumor Models for Drug Discovery

George Church, Ph.D., Professor, Health Sciences and Technology, Harvard and MIT; Founding Core Faculty Member, Wyss Institute for Biologically Inspired Engineering, Harvard University

Anna Collén, Ph.D., Director, Reagents and Assay Development, AstraZeneca

Kristin Fabre, Ph.D., Scientific Program Manager, NCATS, National Institutes of Health

Meir Glick, Ph.D., Head, In Silico Lead Discovery, Center for Proteomic Chemistry, Novartis

Geraldine A. Hamilton, Ph.D., Senior Staff Scientist, Wyss Institute for Biologically Inspired Engineering, Harvard University

Jing Li, Ph.D., Director, Genomics and Phenotypic Screening, Merck

Alan H. Wells, M.D., D.M.Sc., Vice Chair and Thomas J. Gill III Professor, Pathology, University of Pittsburgh

John P. Wikswo, Ph.D., Founding Director, Vanderbilt Institute for Integrative Biosystems Research and Education and Gordon A. Cain University Professor, Biomedical Engineering, Vanderbilt University

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DINNER SHORT COURSES *SUNDAY EVENING, NOV. 16 6:00-9:00 PM

(SC1) Introduction to High-Content Phenotypic ScreeningThe ever-increasing demand for improved productivity in research through the generation of robust analysis outputs has driven both the development and deployment of automated high-content analysis (HCA) and phenotypic cell-based approaches to drug discovery. In contrast to the more traditional cellular analysis and target-based approaches, here the researcher is able to evaluate the efficacy of potential therapeutics by monitoring the physiological state of cells through the simultaneous analysis of multiple cellular parameters in the context of an intact biological system. This course will cover the key features of HCS/A technologies and the best approaches to using these technologies for phenotypic cell-based screening.Instructor:Anthony M. Davies, Ph.D., Center Director, Translational Cell Imaging Queensland (TCIQ), Institute of Health Biomedical Innovation, Queensland University of Technology

(SC2) Exploring 3D Printing, Bioinks and ScaffoldsThe promise of 3D bioprinting to create human tissues layer by layer is immense, ranging from basic biological research to drug development and testing, and ultimately to replacement organs. However, organ and tissue structures vary in complexity, and printing with living cells to create tissues is much more complicated than printing 3D objects in plastic.Instructors:

Future Medical Applications in 3D Printing: Clinical Benefits, Regulatory Issues and Manufacturing ChallengesMichael Drues, Ph.D., President, Vascular Sciences

Multimaterial 3D BioprintingDavid Kolesky, Research Scientist, Jennifer Lewis Laboratory, School of Engineering and Applied Sciences and Wyss Institute for Biologically Inspired Engineering, Harvard University

The Organovo 3D Bioprinting Platform: Changing the Shape of Medical Research and PracticeDeborah G. Nguyen, Director, R&D, Tissue Applications, Organovo, Inc.

Additional Instructors to be Announced

MONDAY EVENING, NOV. 17 6:30-9:30 PM

(SC3) Stem Cell Models for Drug DiscoveryInstructors:Induced Pluripotent Stem Cell-Based Disease Models in Drug DiscoveryAnne G. Bang, Ph.D., Director, Cell Biology, Prebys Center, Sanford-Burnham Medical Research Institute

Human Intestinal Epithelium Derived from Induced Pluripotent Stem CellsPamela J. Hornby, Ph.D., Senior Scientific Director and Research Fellow, Cardiovascular and Metabolic Disease, Translational Models, Janssen Pharmaceutical Companies of Johnson & Johnson

Application of Patient Neuronal Cells Differentiated from iPS Cells as Disease Models for Phenotypic ScreeningWei Zheng, Ph.D., Group Leader, National Center for Advancing Translational Sciences, National Institutes of Health

(SC4) Engineering Microfluidic Cell Culture ChipsMicrofluidic technology holds great promise for the creation of advanced cell culture models. Engineering a microfluidic cell culture chip to emulate the dynamic physiology of a tissue’s microenvironment is paramount for primary cell culture and co-culture. As the availability of functional human cell types for in vitro culture increases, a microfluidic cell culture chip platform’s potential to produce an in vitro system capable of accurately reproducing acute and chronic human responses to drug and pathological challenges in real time will also increase.Instructors:

The Basics of Integrating Cells with Microfluidic Devices for Long-Term Cell Survival and Function in Organ-on-a-Chip DevicesJames J. Hickman, Ph.D., Professor, NanoScience Technology, Chemistry, Biomolecular Science and Electrical Engineering, University of Central Florida

Fabricating a Liver Tissue Model in Microfluidic PlatformsRohit Jindal, Ph.D., Instructor, Surgery, Center for Engineering in Medicine, Massachusetts General Hospital

Additional Instructors to be Announced

TUESDAY EVENING, NOV. 18 6:00-9:00 PM

(SC5) Expert ThinkTank: How to Meet the Need for Physiologically-Relevant Assays?It used to be adequate to build target-specific and robust assays to drive lead optimization. These assays were relatively inexpensive and reliable and could be counted on to provide chemists with usable results. However, with time, it has become apparent that it is not enough to be robust and target specific. To build therapies for patients, we need to have assays that are more predictive of patient outcome. The current buzz words are “physiologically-relevant assays.” This session will explore the need for physiologically-relevant assays and explore the ways that we can achieve this endpoint.Moderator:Lisa Minor, Ph.D., President, In Vitro Strategies, LLCPanelists:• Beverley Isherwood, Ph.D., Team Leader,

AstraZeneca R&D• Michael Jackson, Ph.D., Senior Vice

President, Drug Discovery and Development, Conrad Prebys Center for Chemical Genomics, Sanford-Burnham Medical Research Institute (tentative)

• Jean-Louis Klein, Ph.D., Principal Scientist, Target and Pathway Validation, Platform Technology and Science, GlaxoSmithKline

• Caroline Shamu, Ph.D., Director, ICCB-Longwood Screening Facility and Assistant Professor, Harvard Medical School

• D. Lansing Taylor, Ph.D., Director, University of Pittsburgh Drug Discovery Institute and Allegheny Foundation; Professor, Computational and Systems Biology, University of Pittsburgh

• Scott S. Verbridge, Ph.D., Assistant Professor, School of Biomedical Engineering and Sciences, Virginia Tech – Wake Forest University

*Separate registration required. For further information please visit FASTCongress.com.

Pre-Conference Webinar *Tuesday, September 23

Future Medical Applications in 3-D Printing:Clinical Benefits, Regulatory Issues & Manufacturing Challenges TM

1:00-2:30 pm

Instructor: Michael Drues, Ph.D., President, Vascular Sciences For further information please visit FASTCongress.com *Separate registration required

Gain Further Exposure: Present a Poster and Save $50

• Your poster will be available to 250+ delegates

• You’ll automatically be entered into our poster competition where two winners each will receive an American Express Gift Certificate

• $50 off your registration fee• Your research will be seen by leaders

from pharmaceutical, biotech, academic and government institutes

• Your research abstract will be published in the conference proceedings

• Please visit FASTCongress.com for poster instructions and deadlines

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Phenotypic screening (aka classical pharmacology) has been historically used in drug discovery. While technological developments have made the prevalence of target-based screening more popular, statistical analysis shows that a disproportionate number of first-in-class drugs with novel mechanisms of action come from phenotypic screening. Cambridge Healthtech Institute’s Second Annual Phenotypic Drug Discovery meeting will address the advantages of phenotypic screening vs. target-based screening, and focus on assay development, selection of physiologically-relevant models and subsequent target identification.

Second Annual

Phenotypic Drug Discovery - Part IMaximizing Information in Early Drug Discovery for Better Target and Drug Selection

NOVEMBER 17-18, 2014

SUNDAY, NOVEMBER 16

5:00 pm Short Course Registration and Main Conference Pre-Registration

RECOMMENDED PRE-CONFERENCE SHORT COURSE*6:00-9:00 (SC1) Introduction to High-Content Phenotypic Screening*Separate registration required. See page 3 for details.

MONDAY, NOVEMBER 17

7:30 am Conference Registration and Morning Coffee

CASE STUDIES IN PHENOTYPIC DRUG DISCOVERY

8:00 Chairperson’s Opening RemarksRegis Doyonnas, Ph.D., Pfizer

8:10 Phenotypic Drug Discovery Advances toward Pharmacological Chaperone TherapiesRegis Doyonnas, Ph.D., Senior Principal Scientist, High-Content Screening and HTS-Flow Cytometry, Hit Discovery and Lead Profiling, Worldwide Research & Development, PfizerPharmacological chaperones correct the proper folding of misfolded proteins protecting them from degradation and allowing them to correctly localize within the cell. For many years, drug discovery assays have focused on direct binding of pharmacological chaperones to their protein targets. The relative success of this approach has been called to question with the increasing discussion and analysis of the merits of phenotypic screening. While pharmacological chaperone assays may not lend themselves as “canonical” phenotypic screens, i.e., an assay for direct disease associated outcomes, a case can be made that broadening the analysis to a biological read-out resulting from chaperone activities within a cellular environment would reflect more of the pertinent biology of the system and thus increase our level of confidence in translation to patients.

»KEYNOTE PRESENTATIONS8:35 Phenotypic Screening: A New PerspectiveJing Li, Ph.D., Director, Genomics and Phenotypic Screening, Merck Research LaboratoriesTwo general approaches of drug discovery, either target-centric or phenotypic, are usually taken. Interestingly, in the first-in-class drug category, the phenotypic approach yielded more approved drugs than the target-centric approach during the period 1999-2008. The lack of chemistry support and the immaturity of technology platforms for protein target identification have contributed to the low success rate for past phenotypic screens. Recent advances in the fields of affinity capture, quantitative mass spectrometry, and chemoinformatics greatly improve our chances to identify the underlying protein targets. This provides us opportunities to revisit this subject. With the lessons learned, the possibility of successfully applying phenotypic screens in drug discovery can improve significantly.

9:00 Phenotypic Discovery at AstraZenecaAnna Collén, Ph.D., Director, Reagents and Assay Development, AstraZeneca R&D, Mölndal, SwedenA key denominator for successful phenotypic screening is the translational link of the in vitro cell systems and assays to eventually mimic human physiology. This will direct the positive outcome of the phenotypic screen and enable target identification of relevance to drug discovery. We will present how we at AstraZeneca have worked with phenotypic discovery in different areas: neuroscience with ApoE phenotypic screen, regenerative medicine, cardiac regeneration, islet health and finally identification with factors that differentiate white adipocytes to “brownish.”

9:25 Identification and Optimization of a Novel Phenotype Screen Hit to the First-in-Class HCV NS5A Inhibitor DaclatasvirMakonen Belema, Ph.D., Principal Scientist, Virology Chemistry, Bristol-Myers SquibbHigh-throughput screening of the BMS compound collection afforded a mechanistically unique thiazolidinone hit exhibiting a sub-micromolar inhibitory potency towards an HCV replicon. Raising and mapping of resistance mutation indicated that the NS5A protein, a key protein with a multifunctional role in the virus’ replication cycle, was the most likely target. Highlights of the medicinal chemistry campaign that optimized this screen hit to the highly potent first-in-class HCV NS5A inhibitor daclatasvir along with key clinical results will be discussed. In addition, aspects of the mechanistic study that not only corroborated target engagement but also resulted in the discovery of a class of NS5A-targeting molecules that synergize the inhibitory potency of daclatasvir toward resistant mutants will be covered.

9:50 Sponsored Presentation (Opportunity Available)10:05 Coffee Break in the Exhibit Hall with Poster Viewing10:35 Factors Important to a Successful Phenotypic Screening StrategyDavid C. Swinney, Ph.D., CEO, Institute for Rare and Neglected Diseases Drug Discovery (iRND3)Phenotypic assays are essential tools for drug discovery, with different endpoints depending on the goals: 1) empirical endpoints to understand the underlying biology, 2) empirical endpoints to identify toxicity of drug candidates, and 3) knowledge-based endpoints (biomarkers) to guide discovery which are ideally translational. The value of phenotypic assays is increased through effective alignment of phenotypic assay endpoints with the objectives of the relevant R&D stage.

11:00 Heterogeneity in Drug Discovery, Development and DiagnosticsD. Lansing Taylor, Ph.D., Director, University of Pittsburgh Drug Discovery Institute and Allegheny Foundation Professor, Computational and Systems Biology, University of Pittsburgh11:25 Integrating Novel Technologies to Identify Small Molecules that Drive Translational Research and TherapeuticsMichelle Palmer, Ph.D., Co-Director, Center for the Development of Therapeutics, Broad Institute of Harvard and MITAdvances in human genetics have lead to new drug discovery strategies that may lower the rate of attrition when translated to human trials. Molecular characterization of patient-derived samples is providing new insights into the root cause of many diseases. Many of these insights point to targets that have traditionally been challenging for small-molecule therapeutics. Identification of drugs to modulate targets where knowledge of the function in disease is poorly understood and processes such as disruption of these novel targets require

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innovation in chemistry, phenotypic cell-based assays and target identification studies. At the Broad Institute, we have integrated technology across all aspects of lead identification in an effort to realize the benefit of the genes to drugs approach in multiple disease areas including psychiatric disease. Examples that illustrate the application of novel targets and pathways in a phenotypic screening approach will be presented.

11:50 Close of Session

12:00 pm Luncheon Presentation: Sponsored by Phenotypic Screening of Compounds and Drug Combinations in BioMAP® Oncology Systems Reveals Divergent Effects on Clinically-Relevant BiomarkersScott Pattison, Ph.D., Director, Business Development, DiscoveRx, BioSeek DivisionBioMAP® Oncology Systems model host-tumor microenvironments using human primary fibroblasts or endothelial cells co-cultured with PBMC and select cancer cell lines. The signaling environment modeled therein significantly impacts drug activity on clinically relevant biomarkers. Consistent with clinical reports, we detect enhanced activities with the combination of Dabrafenib (BRAF inhibitor) and Trametinib (MEK inhibitor) as compared to the respective monotherapies. BioMAP® oncology systems provide a predictive human model to assess therapeutic strategies prior to clinical testing.

HIGH-CONTENT ANALYSIS1:30 Chairperson’s RemarksAnne E. Carpenter, Ph.D., Broad Institute of Harvard and MIT1:35 Advancing Drug Discovery through the Application of High-Content Phenotypic ProfilingBeverley Isherwood, Ph.D., Team Leader, AstraZeneca R&DHigh-content analysis (HCA) has developed into an important platform for drug discovery. We describe approaches taken at AstraZeneca to develop and implement multiparametric high-content assay panels in physiologically-relevant models of disease to identify and validate targets, predict toxic liability and characterize compound mode of action. We discuss the tools and workflows adopted to facilitate the efficient, consistent and reliable application of HCA at multiple stages of drug discovery.

2:00 High-Content Imaging Workflows for Screening and Assay Development in Oncology Drug DiscoveryJoern Hopke, Ph.D., Senior Research Investigator, SanofiHigh-content imaging and phenotypic screening create distinctive challenges for data management and subsequent data analysis. We have assembled an array of data management, processing and analysis tools into efficient and flexible workflows for large-scale HCS and small-scale assay development alike. Examples of a screening campaign with successive multivariate data analysis for compound MOA deconvolution and a number of phenotypic 3D assays relevant to oncology drug discovery will be presented.

2:25 Advancing Phenotypic Drug Discovery in Cancer through Combined High-Content Imaging and Reverse Phase Protein Array TechnologyNeil Carragher, Ph.D., Principal Investigator, Edinburgh Cancer Research UK Centre, University of EdinburghLimited understanding of drug mechanism-of-action and pharmacological resistance contributes to poor efficacy and attrition at later stages of drug discovery and development. We demonstrate how multiparametric high-content imaging and Reverse Phase Protein Microarray (RPPA) technologies can combine to enable a robust and unbiased approach to profiling compound mechanism-of-action and optimizing efficacy within complex in vitro and in vivo settings. We will provide case studies demonstrating how we have applied these technologies to advanced models of cancer to progress new chemical entities identified initially as hits from phenotypic screens towards late-stage preclinical development.

2:50 Sponsored Presentation (Opportunity Available)3:05 Refreshment Break in the Exhibit Hall with Poster Viewing3:45 Discovering Unexpected Phenotypes Using Image-Based ProfilingAnne E. Carpenter, Ph.D., Director, Imaging Platform, Broad Institute of Harvard and MITMicroscopy images contain rich information about the state of cells, tissues and organisms. Our laboratory is extracting patterns of morphological perturbations (“signatures”) from images in order to identify similarities between various chemical or genetic treatments. Our goal is to classify drug mechanisms of efficacy and toxicity, distinguish cancer-relevant proteins, and identify

biomarkers of disease. We hope to make perturbations in cell morphology as computable as other large-scale functional genomics data.

4:10 Advances in Phenotypic HTS Reporter Assays and Opportunities for Underserved DiseaseJames Inglese, Ph.D., National Center for Advancing Translational Sciences, National Institutes of HealthEmerging sophistication in assays developed to model pathogenic pathways has the potential to reveal new insights regarding possible routes to pharmacological intervention and in some cases directly to clinical candidates from the repositioning of approved drugs. Specific examples from my lab at NIH focused on assay development and high-throughput screening will be discussed to illuminate these ideas in the context of disease foundation-sponsored collaborative partnerships.

4:35 The Implementation of Phenotypic Cell-Based Assays and High-Content Imaging in Translational Research: Choosing the Right Tools for the JobAnthony M. Davies, Ph.D., Center Director, Translational Cell Imaging Queensland (TCIQ), Institute of Health Biomedical Innovation, Queensland University of Technology

5:00 Sponsored Presentation (Opportunity Available)

5:15 Welcome Reception in the Exhibit Hall with Poster Viewing

6:15 Short Course Registration

RECOMMENDED DINNER SHORT COURSE*6:30-9:30 (SC3) Stem Cell Models for Drug Discovery*Separate registration required. See page 3 for details.

TUESDAY, NOVEMBER 18

8:00 am Breakfast Technology Showcase (Sponsorship Opportunities Available) or Morning Coffee

PHENOTYPIC DRUG DISCOVERYThis showcase provides an opportunity for sponsoring companies to showcase their new and emerging technologies for phenotypic screening, including novel assays, high-content and imaging technologies, physiologically-relevant cellular models and data analysis tools.

8:00 Showcase #18:20 Showcase #28:40 Showcase #3

COMPLEX PHYSIOLOGICALLY-RELEVANT CELLULAR MODELS FOR PHENOTYPIC DRUG DISCOVERY

9:00 Chairperson’s RemarksMichael Jackson, Ph.D., Sanford-Burnham Medical Research Institute9:05 Use of Patient-Derived Cells in Disease-in-a-Dish Phenotypic ScreensMichael Jackson, Ph.D., Senior Vice President, Drug Discovery and Development, Conrad Prebys Center for Chemical Genomics, Sanford-Burnham Medical Research InstituteReprogramming of somatic cells to induced pluripotent stem cells (iPSC) has enabled a new paradigm in drug discovery that leverages disease-in-a-dish phenotypic screens. Technical challenges in the scalability and reproducibility of assays based on iPS (patient) cells remain a major hurdle in executing such screens, especially where mature differentiated cell types are required. Progress on the use of this approach to identify drugs (repurposed) to treat genetic disease will be presented.

9:30 Phenotypic Screening for Alzheimer’s Disease Drug Discovery in Stem Cell-Derived and Primary Brain CellsTae-Wan Kim, Ph.D., Associate Professor, Pathology and Cell Biology, Columbia University Medical CenterThe development of effective and safe therapeutics for complex neurodegenerative diseases, such as Alzheimer’s disease (AD) is hampered in part by lack of physiological cell models. We will discuss our progress on phenotypic, high-throughput screening platforms targeting key AD-relevant cellular pathways (i.e. tau, amyloid and apoE) in primary and stem cell-derived

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Second Annual

Phenotypic Drug Discovery - Part IIMaximizing Information in Early Drug Discovery for Better Target and Drug Selection

NOVEMBER 18-19, 2014

TUESDAY, NOVEMBER 1812:00 pm Conference Registration

PHENOTYPIC SCREENING OF 3D MODELS1:30 Chairperson’s Opening RemarksAron Jaffe, Ph.D., Novartis Institutes for BioMedical Research

1:35 Developing and Utilizing 3D Culture Systems for Novel Target DiscoveryAron Jaffe, Ph.D., Senior Investigator, Developmental and Molecular Pathways, Novartis Institutes for BioMedical ResearchTarget identification and validation have historically relied on immortalized or tumor cell lines grown on plastic. Recent techniques involving growth of cells in three-dimensional matrices have enabled modeling of cellular processes in an environment that more closely resembles the in vivo setting. This presentation will highlight the strategies for designing complex cellular assays for target discovery using medium and high-throughput screening methods in three dimensions.

2:00 3D versus 2D: Insight from Pharmacology and GenomicsJean-Louis Klein, Ph.D., Principal Scientist, Target and Pathway Validation, Platform Technology and Science, GlaxoSmithKline

2:30 Technology Showcase (Sponsorship Opportunities Available)

3D CELLULAR MODELS FOR DRUG AND TARGET SCREENING

This showcase provides an opportunity for sponsoring companies to showcase their new and emerging 3D cell models and technologies for the next generation of drug and target phenotypic screening.

2:30 High-Throughput Compatible Co-Spheroid Model Analyzing Compound Effects on Both Tumor and Stroma Cells Sponsored by

Jan E. Ehlert, Ph.D., Head, Cellular Drug Discovery, ProQinase GmbHA spheroid-based co-culture system for the simultaneous analysis of compound effects on the proliferation of tumor as well as of stroma cells was established. The modular HTS-compatible system reveals results reflecting cell-specific drug susceptibility and cell/cell interactions.

2:50 Showcase #23:10 Showcase #3

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

HIGH-CONTENT ANALYSIS OF TUMOR SPHEROID MODELS4:25 Chairperson’s RemarksDavid Nolte, Ph.D., Professor, Physics, Purdue University; President, Animated Dynamics, Inc.

4:30 Drug Discovery and Development of Novel Anticancer Agents: Applications of Novel 3D Multicellular Tumor Spheroid ModelsDaniel V. LaBarbera, Ph.D., Assistant Professor, Drug Discovery and Medicinal Chemistry, The Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of ColoradoAberrant regulation of epithelial-mesenchymal transition (EMT) is a driving force in the most prominent human diseases. In particular, EMT-driven tumor progression promotes the expansion of cancer stem cells, drug resistance, and the mesenchymal phenotype, which is invasive with a high metastatic potential. Therefore, one therapeutic strategy to prevent metastatic dissemination is to develop small molecule drugs that can revert the mesenchymal phenotype to the more benign epithelial state. Using novel 3D multicellular tumor spheroid (MCTS) models of EMT, suitable for high-throughput and high-content screening (HTS/HCS), we have identified lead compounds that block TCF-transcription, which regulates the mesenchymal phenotype in colorectal cancer.

4:55 Novel Stromal Targets that Support Tumor Spheroid FormationShane R. Horman, Ph.D., Research Investigator, Advanced Assay Group, Genomics Institute of the Novartis Research FoundationThe stroma of solid organ tumors influences all phases of tumor progression indicating that environment may be dominant to the genetics of cancer cells. To expand these concepts to early stage drug discovery we have scrutinized the interactions between colon stroma and colorectal carcinoma (CRC) cells in a high-content co-culture 3D spheroid screen. Subsequently we were able to identify novel fibroblast genes that, when depleted, abrogate CRC spheroid formation revealing an extended chemotherapeutic space by which to target tumors.

5:20 Developing Biodynamic Screening Assays for 3D Live-Tissue ModelsDavid Nolte, Ph.D., Professor, Physics, Purdue University; President, Animated Dynamics, Inc.Biodynamic screening performs three-dimensional functional imaging of living tissue by measuring drug-induced changes in intracellular dynamics.

neurons and glial cells. Our approach will facilitate preclinical discovery of promising therapeutic lead molecules for AD drug discovery.

10:05 Coffee Break in the Exhibit Hall with Poster Viewing10:45 Human Bronchial Epithelial Cells as a Phenotypic Model in Cystic Fibrosis Drug DiscoveryTim Young, Ph.D., Research Fellow, Vertex PharmaceuticalsCystic fibrosis (CF) is caused by mutations in the CFTR gene, which result in decreased ion and fluid transport across bronchial epithelium. Human bronchial epithelial (HBE) cells grown in culture at an air-liquid interface retain the phenotype of airway epithelium with respect to ion and fluid transport, and mucociliary biology. HBEs derived from subjects with CF are impaired in these functions and offer a phenotypic model to develop CFTR modulators.

11:10 Zebrafish Phenotypic Discovery for Small Molecules that Augment Kidney RegenerationAndreas Vogt, Ph.D., Associate Professor, Computational and Systems Biology, University of PittsburghKidney regeneration after acute injury (AKI) is limited by formation of fibrotic scar tissue. Through zebrafish phenotypic screening we identified small molecules that prevent scarring and augment kidney regeneration after injury. Transcriptional profiling suggested a cellular mechanism involving aberrant cell cycle progression, which was confirmed experimentally in zebrafish and mice. The data illustrate the utility of a zebrafish quantitative systems pharmacology approach to discover new potential treatments for AKI.

11:35 Cancer Drugs on the Fly: Whole-Animal Chemical Screening in Drosophila Identifies Drug Interactions with Stem Cells, Stem Cell Tumors and the Stem Cell MicroenvironmentMichele Markstein, Ph.D., Assistant Professor, Biology, UMass AmherstHere we report the development of an in vivo chemical screening platform using tumor models in the adult Drosophila intestine to study the interaction of stem cells with drugs. Strikingly, we find that some FDA-approved chemotherapeutics that can inhibit the growth of Drosophila stem cell tumors can paradoxically promote the hyper-proliferation of their wild type counterparts. These results reveal an unanticipated side effect on stem cells that may drive tumor recurrence. We show that this side effect is mediated by the stem cell microenvironment, which we demonstrate responds to a wide spectrum of chemotherapy drugs. We propose that the same side effect may occur in humans based on our finding that it is driven by the evolutionarily conserved JAK-STAT pathway. To identify additional compounds that can inhibit tumors without inducing side effects on the stem cell microenvironment, we screened a library of 6,100 small molecules, from which we report the identification of 10 compounds that inhibit tumors without inducing the growth promoting side effect. Altogether, our results highlight the importance of using in vivo models to study the effects of drugs on stem cells: we show that the impact of a chemotherapy drug on the stem cell microenvironment is just as important as its impact on the stem cell itself.

12:00 pm Close of Phenotypic Drug Discovery - Part I Conference

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It is compatible with many 3D tissue formats, including tumor spheroids grown in bioreactors or in multiwell plates, as well as tissue biopsies and other organotypic models. Dynamics-based phenotypic profiling of tissues provides a new type of high-content screening. This talk presents 3D assays being developed for chemosensitivity and resistance, proliferation and toxicity screening.

5:45 Close of Day5:45 Short Course Registration

RECOMMENDED DINNER SHORT COURSE*6:00-9:00 (SC5) Expert ThinkTank: How to Meet the Need for Physiologically-Relevant Assays?*Separate registration required. See page 3 for details.

WEDNESDAY, NOVEMBER 197:30 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

PHENOTYPIC DATA ANALYSIS AND MODELING8:00 Chairperson’s RemarksCaroline Shamu, Ph.D., Director, ICCB-Longwood Screening Facility and Assistant Professor, Harvard Medical School

8:10 Cellular Assays for Cancer PharmacologyCaroline Shamu, Ph.D., Director, ICCB-Longwood Screening Facility and Assistant Professor, Harvard Medical SchoolA major goal of the Harvard Medical School Library of Integrated Network-based Cellular Signatures (LINCS) Center is to collect and disseminate the data and analytical tools needed to understand how human cells respond to perturbations created by exposure to drugs. Our center has developed assays to systematically query cell responses to kinase inhibitors and tools to analyze and visualize the results.

»KEYNOTE PRESENTATION8:35 In silico Lead Finding through Holistic Understanding of Screening Data from Multiple ApproachesMeir Glick, Ph.D., Head, In Silico Lead Discovery – Cambridge, Center for Proteomic Chemistry, Novartis Institutes for BioMedical ResearchThe changing drug discovery environment presents a richer, more complicated and novel data landscape. How can state of the art data analytics increase the probability of a lead compound to be disease relevant? We will discuss how in silico approaches actively shape the lead discovery process: informing on relevant assays, compounds subset design to probe the biology, visualization of complex biological data, models elucidating target/MOA hypothesis and design of chemical matter.

9:00 Big Data Tools for High-Content ScreensRajarshi Guha, Ph.D., Research Informatics Scientist, Center for Translational Therapeutics, National Institutes of HealthIn this talk I will provide an overview of the Hadoop ecosystem, an infrastructure designed for parallel processing of large datasets. Specifically,

I will focus on the use of the Mahout library that enables large-scale machine learning on top of Hadoop for the clustering of cell-level data from high-content RNAi screens. I will then describe a backend infrastructure that links HBase, a relational database layer on top of Hadoop, with a traditional Oracle data store to explore and visualize the cell-level clustering.

9:25 Sponsored Presentation (Opportunity Available)9:50 Coffee Break in the Exhibit Hall with Poster Viewing10:45 Chairperson’s RemarksCaroline Shamu, Ph.D., Director, ICCB-Longwood Screening Facility and Assistant Professor, Harvard Medical School

10:50 Automated Learning of Perturbation ModelsRobert F. Murphy, Ph.D., Ray and Stephanie Lane Professor of Computational Biology and Professor of Biological Sciences, Biomedical Engineering and Machine Learning; Director, Lane Center for Computational Biology, Carnegie Mellon UniversityTraditional HCS methods detect perturbed phenotypes but do not allow identification of the specific changes in cell organization underlying them; results also cannot be easily compared across different HCS systems. We developed methods to convert images into models of cell components and how perturbagens affect them, and have also demonstrated that active machine learning can build models of the effects of many drugs on many targets without exhaustive experimentation.

11:15 An Evolutionary Dynamics Approach to Studying Tumor ResistanceArijit Chakravarty, Ph.D., Director, Modeling and Simulation, Takeda Pharmaceuticals

11:40 Towards Open Source Software for High-Content Screening and Phenotypic Data AnalysisFrans Cornelissen, Principal Scientist, Translational Informatics, Janssen Pharmaceutical Companies of Johnson & JohnsonA crucial step towards efficient mining of HCS data is the availability of a robust platform for HCS data management and (semi-)automatic cellular phenotype identification and classification. However, for many small and medium-size screening groups, commercial software may be too expensive. We are in the process of making our internally developed Phaedra software available as an open source product. Examples will be presented to show that Phaedra is a sound foundation that can be used as an integrated pattern recognition and machine learning environment for HCS.

12:05 Genome-Wide RNAi-Compound Epistasis to Elucidate Drug PathwaysJeremy L. Jenkins, Ph.D., Senior Investigator, Developmental and Molecular Pathways, High-Throughput Biology, Novartis Institutes for BioMedical ResearchFollowing phenotypic compound screening, target elucidation remains a bottleneck for follow-up. We investigate examples of genome-wide siRNA screening in the presence of sensitizing compound doses in order to find nodes that sensitize or suppress drug activity and map ‘compound-effect’ pathways. Epistatic shifts in drug activity are observed by intended target knockdown as well as siRNA off-target knockdown caused by miRNA-like polypharmacology of unintended siRNA seed sequence binding to mRNA 3’UTRs.

12:30 pm Close of Phenotypic Drug Discovery - Part II Conference

MEDIA PARTNERS

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Drug Safety Executive CouncilSafer Medicines. Faster.

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Functional 3D models have quickly captured the attention of the pharmaceutical industry. All agree these 3D models offer high content, high impact and high value. However, for wider implementation in R&D drug testing and screening labs, compatible higher-throughput 3D model platforms must be engineered to carry out research on the scale appropriate for drug discovery. Creating these more biologically relevant models requires a multidisciplinary approach and multidisciplinary expertise. Cambridge Healthtech Institute’s Third Annual Engineering Functional 3D Models meeting weaves together engineers, biologists, screening managers and pharmacologists. As with any model, each specialty provides insights into the complete system advancing drug discovery and development.

Third Annual

Engineering Functional 3D ModelsNew Dimensions in the Dynamic Interaction between Drugs and Disease

NOVEMBER 17-18, 2014

SUNDAY, NOVEMBER 165:00 pm Short Course Registration and Main Conference Pre-Registration

RECOMMENDED PRE-CONFERENCE SHORT COURSE*6:00-9:00 (SC2) Exploring 3D Printing, Bioinks and Scaffolds*Separate registration required. See page 3 for details.

MONDAY, NOVEMBER 177:30 am Conference Registration and Morning Coffee8:15 Welcome and Chairperson’s Opening Remarks (Sponsorship Opportunity Available)

»KICKOFF KEYNOTE PRESENTATION8:25 Personalized Reading and Writing of OrgansGeorge Church, Ph.D., Professor, Genetics, Harvard Medical School; Professor, Health Sciences and Technology, Harvard and MIT; Founding Core Faculty Member, Platform Lead, Synthetic Biology, Wyss Institute for Biologically Inspired Engineering, Harvard UniversityWe need better systems for testing small molecule, protein and nucleic acid therapeutics—ideally personalized organs, as can be achieved via iPSC, ePSC or SCNT-ESCs. One or more variants of unknown significance can be tested for a causal role by using CRISPR genome editing and a variety of simple cell types and complex organs and systems derived by epigenomic reprogramming. This engineering system is especially useful in leveraging the world’s only open-access (with very well-characterized -omic and medical data) human subjects (personalgenomes.org). The faithfulness of the organ system models, as well as their drug responses, can be checked using fluorescent in situ sequencing (FISSEQ).

ENGINEERING TISSUE CHIPS AND INTEGRATING ORGAN SYSTEMS

9:05 Models of Complex Human Disease in 3D Skin-Like TissuesJonathan Garlick, D.D.S, Ph.D., Professor, Oral Pathology, School of Dental Medicine, Tufts University; Director, Center for Integrated Tissue Engineering and Professor, Tufts School of Medicine, School of Engineering and Sackler School of Graduate Biomedical SciencesChronic diseases like diabetes are characterized by complex microenvironments in which disease complications arise. The screening of novel treatments, like chronic wounds, must use 3D tissue platforms that better mimic in vivo conditions. We describe the development of 3D tissues that mimic non-healing wounds by incorporating cells derived from chronic wounds and iPSCs. This provides “disease in a tissue” platforms that can more efficiently translate in vitro findings into clinical applications.

9:35 Toward a 3D Model of Human Brain Development for Studying Gene/Environment InteractionsHelena Hogberg, Ph.D., Research Associate, Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University

Microphysiological systems (MPS) could generate more complex in vitro human models that better simulate organ biology and function. iPSCs allow cellular studies of individuals with different genetic backgrounds. Application of iPSCs from different donors in MPS improves understanding of disease mechanisms, drug development, toxicology and medicine. For a brain-on-a-chip, we established a 3D model from healthy and Down Syndrome donors’ iPSCs with mRNA and microRNA levels evaluated during eight weeks of neural differentiation.

10:05 Coffee Break in the Exhibit Hall with Poster Viewing10:30 “Body-on-a-Chip”: A Multi-Organ Microdevice for Drug DevelopmentMichael L. Shuler, Ph.D., Professor, Chemical Engineering and Chair, Biomedical Engineering, School of Chemical and Biomolecular Engineering, Cornell UniversityOur goal is the development of a human-based in vitro system that reduces dependency on animal testing and makes more effective predictions of human response to drugs. By combining microfabrication and cell culture, we have constructed devices known as “Body-on-a-Chip” systems. These devices are physical replicas of a physiologically based pharmacokinetic (PBPK) model where tissue-engineered constructs replace the differential equations for each organ in the PBPK.

11:00 Organs on a Chip: The Future of Personalized Medicine?Kevin E. Healy, Ph.D., Jan Fandrianto Distinguished Chair in Engineering; Professor and Chair, Bioengineering; Professor, Materials Science and Engineering, University of California, BerkeleyDrug safety and efficacy testing are hampered by high failure rates attributed to reliance on non-human animal models. We have developed integrated in vitro models of human cardiac and liver tissue based on normal and patient-specific hiPS cell populations differentiated into cardiomyocytes or hepatocytes, respectively. Our in vitro integrated physiological system has the potential to significantly reduce both the cost and duration of bringing a new drug candidate to market.

11:30 Sponsored Presentation (Opportunity Available)12:00 pm Close of Session12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

HIGH-DIMENSIONAL TISSUE AND ORGAN MODELS: ADVANTAGES AND DISADVANTAGES OF 2D VS. 3D

1:30 Chairperson’s RemarksRosemarie Hunziker, Ph.D., Director, Tissue Engineering and Regenerative Medicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health

1:35 2D Versus 3D: When to Make the SwitchChristopher S. Chen, M.D., Ph.D., Professor, Biomedical Engineering, Boston University and Wyss Institute for Biologically Inspired Engineering, Harvard UniversityThe structure, mechanics and dimensionality of an extracellular matrix have fundamental effects on the phenotype of mammalian cells. This presentation examines how these physical cues can drive cell signaling and function, and how we can use these insights to develop in vitro cultures that better mimic in vivo biology for both discovery and development applications.

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2:05 Customized 3D Cell Cultures and Assays Showcase (Sponsorship Opportunities Available)All agree that 3D cell models that are morphologically and functionally similar to native tissue hold the potential to improve in vitro cell-based assays. However, it is important to note that there is no one-size-fits-all solution; each cell type requires a different environment and different assays to screen them. This session showcases companies that are driving cell culture and screening assays into the new dimension of studying health vs. disease and drug response.

2:05 Showcase #12:25 Showcase #22:45 Showcase #3

3:05 Refreshment Break in the Exhibit Hall with Poster Viewing

»KEYNOTE PRESENTATIONS3:45 Organs-on-Chips to Screen for Drug Efficacy and ToxicityKristin Fabre, Ph.D., Scientific Program Manager, NCATS, National Institutes of HealthThe Microphysiological Systems Program, comprised of an MPS Consortium of academic and government entities, aims to bioengineer platforms (or chips) that mimic human organ systems. These platforms help predict efficacy and toxicity of candidate compounds faster, cheaper and with fewer animal models than current methods. The project’s goal is to incorporate human iPSC-derived cell sources (inducible pluripotent stem cells) into corresponding organ modules and create an integrated Human-on-a-Chip to study drug response within human bodies.

4:30 Organs-on-Chips: Highly Functional Microphysiological Systems to Predict Human Physiology and PathobiologyGeraldine A. Hamilton, Ph.D., Senior Staff Scientist, Wyss Institute for Biologically Inspired Engineering, Harvard UniversityThis presentation focuses on our novel biomimetic microsystem technologies and their potential application in predicting efficacy, safety and mechanism of action for new drugs, chemicals and cosmetics. Human organs-on-chips provide exciting new approaches to attack fundamental questions in biology and develop smart in vitro surrogates. This technology also offers a more human-relevant alternative to current animal-based approaches for disease model development.

5:15 Welcome Reception in the Exhibit Hall with Poster Viewing6:15 Short Course Registration

RECOMMENDED DINNER SHORT COURSE*6:30-9:30 (SC4) Engineering Microfluidic Cell Culture Chips*Separate registration required. See page 3 for details.

TUESDAY, NOVEMBER 187:30 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

TISSUE MICROENGINEERING TOOLS8:30 Chairperson’s RemarksJonathan Garlick, D.D.S, Ph.D., Tufts University

8:35 Microengineering Hydrogels for Tissue Engineering ApplicationsNasim Annabi, Ph.D., Instructor, Brigham and Women’s Hospital and Harvard Medical SchoolMicro- and nanoscale technologies are powerful techniques in addressing the current challenges in tissue engineering. These technologies have allowed for an unprecedented ability to control cell-microenvironment interactions.

Our group has been actively involved in merging advanced biomaterials and microscale technologies to create 3D vascularized tissues. I outline our work in the development of microscale hydrogels to modulate cell-microenvironment interactions for tissue engineering applications.

9:05 Development of 3D Tissue Engineering Platforms for Personalized Cancer TherapeuticsJenny Zilberberg, Ph.D., Assistant Scientist, The John Theurer Cancer Center, Hackensack University Medical CenterI present work on the development of a novel 3D tissue engineering platform that uses microfluidic technology to provide a physiologically relevant in vitro model to study cancers that reside in or metastasizes to the bone/bone marrow microenvironment, and could offer a suitable tool to perform chemosensitivity analysis and develop new cancer therapeutics.

9:35 Micro- and Nanoscale 3D Bioprinting for Functional Tissue ScaffoldsShaochen Chen, Ph.D., Professor, NanoEngineering and Bioengineering, University of California, San DiegoI discuss my laboratory’s recent research efforts in femtosecond laser nanoprinting and projection 3D bioprinting to create 3D scaffolds using a variety of biomaterials. These 3D biomaterials are functionalized with precise control of microarchitecture, mechanical properties (e.g., stiffness and Poisson’s ratio) and growth factors. Such functional biomaterials allow us to investigate cell-microenvironment interactions at nano- and microscales in response to integrated physical and chemical stimuli.

10:05 Coffee Break in the Exhibit Hall with Poster Viewing10:45 Synthetic Capillaries: Engineering Microscale Blood FlowGregory Timp, Ph.D., Keough-Hesburgh Professor of Engineering and Systems Biology, Colleges of Science and Engineering, University of Notre DameCapillaries pervade human physiology. The lack of perfusion associated with capillaries is especially problematic in thick engineered tissue because it leads to hypoxic stress and necrosis. We show it is possible to create in vitro a microenvironment that emulates a capillary using “live cell lithography” by controlling the type and position of cells on a composite hydrogel scaffold. These constructs support the forces and nutrient gradients associated with blood flow.

11:15 A New 3D Model to Test Clonal Expansion and Treatment Efficacy of Potential Drugs for Multiple MyelomaBhagavathi Narayanan, Ph.D., Associate Professor, Environmental Medicine, NYU School of MedicineMethacrylated hyaluronic acid-based 3D hybrid hydrogel provides a unique ex vivo system that mimics a physiologically similar human microenvironment suitable for examining the behavior of invasive cancer cells. Most important, 3D hydrogel with differences in matrix composition and stiffness represents a new version of 3D model that supports clonal expansion, migration, multiplication and differentiation of cancer cells. Clonal expansion within encapsulated hydrogels enables assessment of the treatment efficacy of potential drugs.

»CLOSING KEYNOTE PRESENTATION11:45 Scaling and Systems Biology for Integrating Multiple Organs-on-a-ChipJohn P. Wikswo, Ph.D., Founding Director, Vanderbilt Institute for Integrative Biosystems Research and Education and Gordon A. Cain University Professor, Biomedical Engineering, Vanderbilt UniversityDetermination of the toxicity of drugs, consumer products and industrial chemicals will benefit from quantitative systems approaches to pharmacology and toxicology. By supporting heterogeneous cell populations and complex 3D extracellular matrices, tissue-engineered organs-on-chips and human organ constructs provide in vitro organotypic culture models for tissue-scale toxicology that are more realistic than static, planar, monolayer, immortal monocultures. Properly coupled, they create a new class of in vitro microphysiological systems models.

12:30 pm Close of Engineering Functional 3D Models and Organotypic Culture Models for Toxicology Conferences

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While more informative than cell-free biochemical assays, monolayer or suspension cell culture HTS assays still fail to accurately reflect the human cellular microenvironment. There is a need for physiologically-relevant cellular models for drug screening and functional analysis that provide high predictive value for clinical efficacy and safety of compounds. The 3-dimensional cell culture models mimic the human tissue microenvironment and provide more accurate information for compound and target selection, thereby reducing late-stage attrition. Cambridge Healthtech Institute’s Second Annual Screening and Functional Analysis of 3D Models meeting will explore the use of 3D models to profile compound action and predict toxicity and efficacy. The meeting will cover assay development using 3D cellular models, high-content analysis and imaging of 3D models, and applications of screening 3D models for compound profiling and target discovery/validation.

Second Annual

Screening and Functional Analysis of 3D ModelsComplex Cellular Models Predictive of Human Response to Improve Early Decision Making

NOVEMBER 18-19, 2014

TUESDAY, NOVEMBER 1812:00 pm Conference Registration

PHENOTYPIC SCREENING OF 3D MODELS1:30 Chairperson’s Opening RemarksAron Jaffe, Ph.D., Novartis Institutes for BioMedical Research

1:35 Developing and Utilizing 3D Culture Systems for Novel Target DiscoveryAron Jaffe, Ph.D., Senior Investigator, Developmental and Molecular Pathways, Novartis Institutes for BioMedical ResearchTarget identification and validation have historically relied on immortalized or tumor cell lines grown on plastic. Recent techniques involving growth of cells in three-dimensional matrices have enabled modeling of cellular processes in an environment that more closely resembles the in vivo setting. This presentation will highlight the strategies for designing complex cellular assays for target discovery using medium and high-throughput screening methods in three dimensions.

2:00 3D versus 2D: Insight from Pharmacology and GenomicsJean-Louis Klein, Ph.D., Principal Scientist, Target and Pathway Validation, Platform Technology and Science, GlaxoSmithKline

2:30 Technology Showcase (Sponsorship Opportunities Available)

3D CELLULAR MODELS FOR DRUG AND TARGET SCREENING

This showcase provides an opportunity for sponsoring companies to showcase their new and emerging 3D cell models and technologies for the next generation of drug and target phenotypic screening.

2:30 High-Throughput Compatible Co-Spheroid Model Analyzing Compound Effects on Both Tumor and Stroma Cells

Sponsored by

Jan E. Ehlert, Ph.D., Head, Cellular Drug Discovery, ProQinase GmbHA spheroid-based co-culture system for the simultaneous analysis of compound effects on the proliferation of tumor as well as of stroma cells was established. The modular HTS-compatible system reveals results reflecting cell-specific drug susceptibility and cell/cell interactions.

2:50 Showcase #23:10 Showcase #3

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

HIGH-CONTENT ANALYSIS OF TUMOR SPHEROID MODELS4:25 Chairperson’s RemarksDavid Nolte, Ph.D., Professor, Physics, Purdue University; President, Animated Dynamics, Inc.

4:30 Drug Discovery and Development of Novel Anticancer Agents: Applications of Novel 3D Multicellular Tumor Spheroid ModelsDaniel V. LaBarbera, Ph.D., Assistant Professor, Drug Discovery and Medicinal Chemistry, The Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of ColoradoAberrant regulation of epithelial-mesenchymal transition (EMT) is a driving force in the most prominent human diseases. In particular, EMT driven tumor progression promotes the expansion of cancer stem cells, drug resistance, and the mesenchymal phenotype, which is invasive with a high metastatic potential. Therefore, one therapeutic strategy to prevent metastatic dissemination is to develop small molecule drugs that can revert the mesenchymal phenotype to the more benign epithelial state. Using novel 3D multicellular tumor spheroid (MCTS) models of EMT, suitable for high-throughput and high-content screening (HTS/HCS), we have identified lead compounds that block TCF-transcription, which regulates the mesenchymal phenotype in colorectal cancer.

4:55 Novel Stromal Targets that Support Tumor Spheroid FormationShane R. Horman, Ph.D., Research Investigator, Advanced Assay Group, Genomics Institute of the Novartis Research FoundationThe stroma of solid organ tumors influences all phases of tumor progression indicating that environment may be dominant to the genetics of cancer cells. To expand these concepts to early stage drug discovery we have scrutinized the interactions between colon stroma and colorectal carcinoma (CRC) cells in a high-content co-culture 3D spheroid screen. Subsequently we were able to identify novel fibroblast genes that, when depleted, abrogate CRC spheroid formation revealing an extended chemotherapeutic space by which to target tumors.

5:20 Developing Biodynamic Screening Assays for 3D Live-Tissue ModelsDavid Nolte, Ph.D., Professor, Physics, Purdue University; President, Animated Dynamics, Inc.Biodynamic screening performs three-dimensional functional imaging of living tissue by measuring drug-induced changes in intracellular dynamics. It is compatible with many 3D tissue formats, including tumor spheroids grown in bioreactors or in multiwell plates, as well as tissue biopsies and other organotypic models. Dynamics-based phenotypic profiling of tissues provides a new type of high-content screening. This talk presents 3D assays being developed for chemosensitivity and resistance, proliferation and toxicity screening.

5:45 Close of Day5:45 Short Course Registration

RECOMMENDED DINNER SHORT COURSE*6:00-9:00 (SC5) Expert ThinkTank: How to Meet the Need for Physiologically-Relevant Assays?*Separate registration required. See page 3 for details.

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WEDNESDAY, NOVEMBER 197:30 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

ENGINEERING COMPLEX 3D MODELS OF TUMOR MICROENVIRONMENT FOR DRUG SCREENING AND

FUNCTIONAL ANALYSIS8:00 Chairperson’s RemarksMary C. Farach-Carson, Ph.D., Rice University

8:10 Targeted Electric Field Therapy Development in 3D Models of the Heterogeneous Glioma MicroenvironmentScott S. Verbridge, Ph.D., Assistant Professor, School of Biomedical Engineering and Sciences, Virginia Tech – Wake Forest University3D tissue models that incorporate the physico-chemo-cellular heterogeneities of human tumors are a valuable tool for the development of treatments targeted against the cells that resist traditional therapies. We will discuss our recent work in targeting the physical properties of therapy resistant brain cancer cells, leveraging 3D models to analyze the impact of cell type and mechanical microenvironment on cellular response to high frequency electric fields.

8:35 Targeting Physical and Stromal Determinants of Tumor Heterogeneity in Bioengineered 3D ModelsImran Rizvi, Ph.D., Instructor, Medicine and Dermatology, Harvard Medical School; Associate Bioengineer, Brigham and Women’s Hospital; Assistant, Biomedical Engineering, Wellman Center for Photomedicine, Massachusetts General HospitalThe biological characteristics and treatment response of cancers is influenced by an array of factors including flow-induced shear stress, stromal partners, and matrix composition, which play deterministic roles in the fate of disseminated tumours. Research platforms that integrate these cues are critically needed to identify mechanism-based combinations. Current findings will be presented on the impact of flow and stromal partners, including tumor endothelial cells, on the biological characteristics of 3D co-cultures, and their susceptibility to conventional and emerging therapies.

9:00 3D Hydrogel Co-Culture Systems for Growing Patient-Derived Xenografts: Use in Selective Drug ScreeningMary C. Farach-Carson, Ph.D., Ralph and Dorothy Looney Professor, Biochemistry and Cell Biology; Scientific Director, BioScience Research Collaborative, Rice UniversityBuilding on success culturing metastatic prostate cancer (PCa) cell lines using 3D HA-based hydrogels, we now can culture ‘never in 2D’ patient-derived xenograft (PDX) tumors alone or with other cells from the tumor microenvironment. Hydrogel-encapsulated PDX tumoroids retain viability over two weeks, proliferate and express androgen receptor, providing a valuable new platform for drug discovery and screening. We now aim to eliminate the ‘middle mouse’– a leap towards personalized medicine.

9:25 Human Stroma-Derived Extracellular Matrices: 3D ECM Physiological SystemsEdna Cukierman, Ph.D., Associate Professor, Cancer Biology, Fox Chase Cancer Center

The talk will describe desmoplasia (i.e., cancer-associated) and fibrosis in vivo-like 3D ECM models. It will highlight the system’s physiologic and pathologic relevance. The seminar will illustrate target validation, phenotype assessment, functional analysis and drug efficacy uses. Assorted tumor-associated microenvironments will showcase tissue patterning, multi-spectra acquisitions and digital imaging analyses together with classic cell biology and biochemistry approaches. Finally, the use of well-annotated human pathological samples will establish clinical applicability.

9:50 Coffee Break in the Exhibit Hall with Poster Viewing

ENGINEERING IN VITRO MODELS OF CANCER METASTASIS10:45 Chairperson’s RemarksAlan H. Wells, M.D., D.M.Sc., University of Pittsburgh

10:50 In vitro Models for Metastatic DiseaseRoger D. Kamm, Ph.D., Cecil and Ida Green Distinguished Professor, Biological and Mechanical Engineering, MIT

11:15 Monitoring Extravascular Migratory Metastasis of Angiotropic Cancer Cells Using a 3D in vitro Co-Culture SystemClaire Lugassy, M.D., Research Associate Professor, Pathology and Lab Medicine, UCLA School of Medicine; Member, Jonsson Comprehensive Cancer CenterDuring extravascular migratory metastasis (EVMM), angiotropic tumor cells migrate along the abluminal vascular surfaces without intravasation (pericytic-mimicry) and may spread to nearby or more distant sites. Our recent publication in Nature confirmed again the importance of this underexplored metastatic pathway. We have developed a fluorescence-based 3D co-culture model to monitor in real time single tumor cell migration/EVMM in a vascular microenvironment. This assay can be adapted for anticancer drug screening.

»KEYNOTE PRESENTATION11:40 An All-Human Microphysiologic Liver System for Carcinoma MetastasisAlan H. Wells, M.D., D.M.Sc., Vice Chair and Thomas J. Gill III Professor, Pathology, University of PittsburghMetastases kill patients, but disseminated cancers are resistant to therapies. The tumor biological events behind this are unknown due to lack of relevant model systems. Further, humans metabolize agents and present toxicities uniquely, hampering drug development. We have developed an all-human microphysiological system of the liver to study both tumor behavior in the common metastatic site, and drug metabolism/efficacy in the main metabolizing organ.

12:05 Using Block Cell Printing to Develop Single Cell Arrays for Drug ScreeningLidong Qin, Ph.D., Associate Member, Nanomedicine, Methodist Hospital Research Institute; Assistant Professor, Cell and Developmental Biology, Weill Cornell Medical College

12:30 pm Close of Screening and Functional Analysis of 3D Models Conference

CHI offers comprehensive packages that can be customized to your budget and objectives. Sponsorship allows you to achieve your goals before, during, and long after the event. Packages may include presentations, exhibit space and branding, as well as the use of delegate lists. Signing on early will maximize your exposure to qualified decision-makers and drive traffic to your website in the coming months.

Podium Presentations – Available with 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!

Invitation-Only VIP Dinner/Hospitality SuiteSelect specific delegates from the pre-registration list to attend a private function at an upscale restaurant or a reception at the hotel. From extending the invitations, to venue suggestions, CHI will deliver your prospects and help you make the most of this invaluable opportunity.

Focus GroupCHI will gladly provide you the opportunity of running a focus group on-site. This exclusive gathering can be useful to conduct market research, collect feedback on a new product idea, and collect marketing intelligence from industry experts on a specific topic.

User Group Meeting / Custom EventCo-locate your user group meeting or custom event. CHI will help market the event, manage logistical operations, develop the agenda, and more. CHI can handle the entirety of the meeting or select aspects.

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 and promotional opportunities are available, including:Conference Tote BagsLiterature Distribution (Tote Bag Insert or Chair Drop)

Badge LanyardsProgram Guide AdvertisementPadfolios and More...

Sponsorship & Exhibit Opportunities

To customize your participation at this event, please contact:Ilana Quigley – Business Development Manager

781-972-5457 | iquigley@healthtech.com

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It is recognized that in vitro toxicology studies are complex. Organotypic culture models (OCMs)—tissue models that mimic in vivo tissue architecture through interactions of heterotypic cell types and extracellular matrices—are increasingly being explored for prediction of organ-specific toxicity. As these models become more widely used for chemical and drug toxicity testing, there is a corresponding need to establish standardized testing conditions, endpoint analyses and acceptance criteria. Cambridge Healthtech Institute’s Inaugural Organotypic Culture Models for Toxicology meeting addresses the balanced approach between sample throughput and biological relevance, providing better in vitro tools to replace animal testing and predict human risk assessment.

Inaugural

Organotypic Culture Models for ToxicologyIn vitro Screening Tools for Modeling and Predicting Organ-Specific Toxicity

NOVEMBER 17-18, 2014

SUNDAY, NOVEMBER 165:00 pm Short Course Registration and Main Conference Pre-Registration

RECOMMENDED PRE-CONFERENCE SHORT COURSE*6:00-9:00 (SC2) Exploring 3D Printing, Bioinks and Scaffolds*Separate registration required. See page 3 for details.

MONDAY, NOVEMBER 177:30 am Conference Registration and Morning Coffee8:15 Welcome and Chairperson’s Opening Remarks (Sponsorship Opportunity Available)

»KICKOFF KEYNOTE PRESENTATION8:25 Personalized Reading and Writing of OrgansGeorge Church, Ph.D., Professor, Genetics, Harvard Medical School; Professor, Health Sciences and Technology, Harvard and MIT; Founding Core Faculty Member, Platform Lead, Synthetic Biology, Wyss Institute for Biologically Inspired Engineering, Harvard UniversityWe need better systems for testing small molecule, protein and nucleic acid therapeutics—ideally personalized organs, as can be achieved via iPSC, ePSC or SCNT-ESCs. One or more variants of unknown significance can be tested for a causal role by using CRISPR genome editing and a variety of simple cell types and complex organs and systems derived by epigenomic reprogramming. This engineering system is especially useful in leveraging the world’s only open-access (with very well-characterized -omic and medical data) human subjects (personalgenomes.org). The faithfulness of the organ system models, as well as their drug responses, can be checked using fluorescent in situ sequencing (FISSEQ).

KIDNEY – NEPHROTOXICITY TESTING STRATEGIES 9:05 A Human Kidney Microphysiological SystemJonathan Himmelfarb, M.D., Director, Kidney Research Institute; Joseph W. Eschbach Endowed Chair in Kidney Research; Professor, Medicine, Division of Nephrology, University of WashingtonWe have designed, implemented and tested a tissue-engineered human kidney microphysiological system. The system is developed to fully evaluate uptake, metabolism and elimination of xenobiotics in a human tissue-derived, in vitro 3-dimensional system that accurately reflects human physiology. The microphysiological system can be used to predict disposition kinetics of xenobiotics and also assess the response to kidney injury inflicted by endogenous and exogenous toxicants.

9:35 Mini-Kidneys Derived from Human Stem CellsJuan Carlos Izpisua Belmonte, Ph.D., Roger Guillemin Chair and Professor, Gene Expression Laboratories, Salk Institute for Biological SciencesHuman pluripotent stem cells hold great promise for the modeling of disease and toxicology studies upon directed differentiation. The kidney represents an architecturally complex organ responsible for blood toxin clearance. Here we discuss how derivation of functional renal structures in vitro can open unprecedented opportunities for the modeling of kidney disease and general toxicology studies.

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

HEART – CARDIOTOXICITY TESTING METHODS10:30 Engineering Macroscale 3D Human Cardiac Tissue from hPSCsKareen Coulombe, Ph.D., Assistant Professor, Engineering, School of Engineering, Brown UniversityRegenerating the heart post-injury requires a large, muscular implant contributing contractile force to aid the heart’s pumping action. We are developing 3D engineered tissues of various geometries using cardiomyocytes derived from human pluripotent stem cells to study tissue architecture, cellular phenotype, passive and active mechanical properties and regeneration in a rat model of myocardial infarction. We focus on vascularization and contractility in vivo and design tissues in vitro for translational applications, including toxicology testing.

11:00 Screening Drug-Induced Arrhythmia Events Using Human-Induced Pluripotent Stem Cell-Derived CardiomyocytesAndrew S. Lee, Ph.D., Co-Founder and CSO, Stem Cell TheranosticsCardiotoxicity is a leading cause of drug attrition during pharmaceutical development and of market withdrawal due to safety concerns. Recent advances in induced pluripotent stem cell (iPSC) technology have allowed the generation of cardiomyocytes that can be used to model drug-induced cardiotoxicity. We describe a novel iPSC platform that utilizes patient-specific cardiomyocytes for personalized prediction of cardiac drug toxicity in patient subpopulations with a history of cardiovascular disease.

11:30 Micro- and Nanotechnologies for 3D Cardiac Tissue Constructs with Functionalized NanoparticlesSu-Ryon Shin, Ph.D., Instructor, Medicine, Harvard Medical SchoolThe development of highly organized and functional 3D complex constructs in vitro is important in tissue engineering. In particular, heart muscles are dense quasi-lamellar and highly vascularized tissues in which functional syncytia of the cardiomyocytes are tightly interconnected with gap junctions. To address these challenges, we are developing a novel approach that combines nanoparticles and microfabrication techniques to create dense and highly organized 3D cardiac tissue constructs with biomimetic electrophysiological function.

12:00 pm Close of Session12:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

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HIGH-DIMENSIONAL TISSUE AND ORGAN MODELS: ADVANTAGES AND DISADVANTAGES OF 2D VS. 3D

1:30 Chairperson’s RemarksRosemarie Hunziker, Ph.D., Director, Tissue Engineering and Regenerative Medicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health

1:35 Organotypic Three-Dimensional Tissue ModelsHeike Walles, Ph.D., Chair and Head, Regenerative Therapies, Tissue Engineering and Regenerative Medicine and Fraunhofer IGB Project Group, University Hospital WürzburgOur group has been committed to the development of alternative human test systems that reflect the body’s complex characteristics. We have succeeded in building up skin equivalents that can be extended by other cells. Moreover, we have established a trachea and an intestine tissue model as different tumor model systems. To ensure culture conditions that are similar to the cells’ natural environment in the body, specific bioreactor systems have been developed.

2:05 Customized 3D Cell Cultures and Assays Showcase (Sponsorship Opportunities Available)All agree that 3D cell models that are morphologically and functionally similar to native tissue hold the potential to improve in vitro cell-based assays. However, it is important to note that there is no one-size-fits-all solution; each cell type requires a different environment and different assays to screen them. This session showcases companies that are driving cell culture and screening assays into the new dimension of studying health vs. disease and drug response.

2:05 Showcase #12:25 Showcase #22:45 Showcase #3

3:05 Refreshment Break in the Exhibit Hall with Poster Viewing

»KEYNOTE PRESENTATIONS3:45 Organs-on-Chips to Screen for Drug Efficacy and ToxicityKristin Fabre, Ph.D., Scientific Program Manager, NCATS, National Institutes of HealthThe Microphysiological Systems Program, comprised of an MPS Consortium of academic and government entities, aims to bioengineer platforms (or chips) that mimic human organ systems. These platforms help predict efficacy and toxicity of candidate compounds faster, cheaper and with fewer animal models than current methods. The project’s goal is to incorporate human iPSC-derived cell sources (inducible pluripotent stem cells) into corresponding organ modules and create an integrated Human-on-a-Chip to study drug response within human bodies.

4:30 Organs-on-Chips: Highly Functional Microphysiological Systems to Predict Human Physiology and PathobiologyGeraldine A. Hamilton, Ph.D., Senior Staff Scientist, Wyss Institute for Biologically Inspired Engineering, Harvard UniversityThis presentation focuses on our novel biomimetic microsystem technologies and their potential application in predicting efficacy, safety and mechanism of action for new drugs, chemicals and cosmetics. Human organs-on-chips provide exciting new approaches to attack fundamental questions in biology and develop smart in vitro surrogates. This technology also offers a more human-relevant alternative to current animal-based approaches for disease model development.

5:15 Welcome Reception in the Exhibit Hall with Poster Viewing6:15 Short Course Registration

RECOMMENDED DINNER SHORT COURSE*6:30-9:30 (SC4) Engineering Microfluidic Cell Culture Chips

*Separate registration required. See page 3 for details.

TUESDAY, NOVEMBER 187:30 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

LIVER AND GUT – HEPATOTOXICITY AND GASTROINTESTINAL TOXICITY TESTING REGIMES

8:30 Chairperson’s RemarksJames J. Hickman, Ph.D., University of Central Florida

8:35 iPSC-Derived Hepatic Model Systems for Investigating Mechanisms of IDILIJingtao Lu, Ph.D., Research Scientist, The Hamner Institutes for Health SciencesInduced pluripotent stem cell-derived hepatocytes (iHC) were assessed as a drug-induced liver injury model. iHCs were comparable to primary human hepatocytes (pHH) in architecture, gene expression profiles, CYP activities and sensitivities to multiple model hepatotoxins. In the study of isoniazid (INH)-induced idiosyncratic liver injury (IDILI), iHCs showed pHH-like sensitivity towards INH-mediated cytotoxicity, protein adduction and mitochondrial toxicity. Combined results support iHCs as a promising new hepatic model to investigate IDILI mechanisms.

9:05 Biomimiks as Chemosynthetic LiversMukund S. Chorghade, Ph.D., CSO, Empiriko CorporationOur proprietary technology mimics metabolism of chemical entities for pharmaceuticals, enables prediction of metabolism patterns and introduces new paradigms for drug discovery and drug-drug interactions. Our catalysts provide speed, stability and scalability. We predict structures of metabolites, prepare them on scale and elucidate chemical structures. Comprehensive safety evaluation enables complete metabolism studies, confirmation of structure and quantitative measures of toxicity. This is an animal-free platform for safety-relevant metabolites.

9:35 Three-Dimensional Human Small Intestine Models for ADME-Tox StudiesJiajie Yu, Ph.D., Research Scientist, Linda Griffith Laboratory, Biological Engineering, Massachusetts Institute of TechnologyIn vitro cell-based human small intestine models have been widely used in drug preclinical development. However, these traditional models could provide misleading results due to their relatively poor recapitulation of small intestine physiology. This presentation focuses on recent breakthroughs of developing more physiological in vitro human small intestine models as well as their impacts on preclinical ADME-Tox studies.

10:05 Coffee Break in the Exhibit Hall with Poster Viewing10:45 Sponsored Presentation (Opportunity Available)11:15 Body-on-a-Chip Systems for Toxicological EvaluationsJames J. Hickman, Ph.D., Professor, NanoScience Technology, Chemistry, Biomolecular Science and Electrical Engineering, University of Central FloridaReplacing animals in toxicology and drug discovery with integrated functional organ constructs in a serum-free defined system composed of human cells will greatly reduce the cost and increase the relevance of these studies. Furthermore, utilizing functional human models in both 2D and 3D systems will facilitate both acute and chronic compound evaluations for toxicological applications that are not currently possible in vitro.

»CLOSING KEYNOTE PRESENTATION11:45 Scaling and Systems Biology for Integrating Multiple Organs-on-a-ChipJohn P. Wikswo, Ph.D., Founding Director, Vanderbilt Institute for Integrative Biosystems Research and Education and Gordon A. Cain University Professor, Biomedical Engineering, Vanderbilt UniversityDetermination of the toxicity of drugs, consumer products and industrial chemicals will benefit from quantitative systems approaches to pharmacology and toxicology. By supporting heterogeneous cell populations and complex 3D extracellular matrices, tissue-engineered organs-on-chips and human organ constructs provide in vitro organotypic culture models for tissue-scale toxicology that are more realistic than static, planar, monolayer, immortal monocultures. Properly coupled, they create a new class of in vitro microphysiological systems models.

12:30 pm Close of Engineering Functional 3D Models and Organotypic Culture Models for Toxicology Conferences

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Traditional drug screening relies on monolayer cell culture, which is not always predictive of natural physiological state. This is especially problematic in cancer drug discovery, where simple cell cultures are not predictive of complex tumor microenvironment that consists of various cell types that interact in 3-dimensional structures. As the cost of drug development rises, there is increasing pressure for more predictive in vitro models for functional analysis and compound characterization. Cambridge Healthtech Institute’s Second Annual Physiologically-Relevant Cellular Tumor Models for Drug Discovery meeting will focus on the latest advances in 3D cellular tumor models and complex co-culture systems for functional analysis studies and compound screening/characterization.

Second Annual

Physiologically-Relevant Cellular Tumor Models for Drug DiscoveryIn vitro Models of Tumor Microenvironment for New Cancer Target and Drug DiscoveryNOVEMBER 18-19, 2014

TUESDAY, NOVEMBER 1812:00 pm Conference Registration

ENGINEERING AND SCREENING TUMOR SPHEROID MODELS

1:30 Chairperson’s Opening RemarksMitchell Ho, Ph.D., National Cancer Institute

1:35 New Tricks for Spheroids: Mimicking Stromal Interactions, Investigating Nanoparticle Drug Delivery, and Modeling ResectionMark Grinstaff, Ph.D., Professor, Chemistry, Boston University

2:00 Functional Analysis of Therapeutic Antibodies and Antigens Using ex vivo Tumor SpheroidsMitchell Ho, Ph.D., Chief, Antibody Therapy Section, Laboratory of Molecular Biology, National Cancer Institute, National Institutes of HealthTumor microenvironments present significant barriers to antibody therapy. We established ex vivo tumor spheroids to study molecular mechanisms of antibody drug resistance. The tumor spheroids may prove invaluable for identifying potential targets in addition to providing an innovative platform for analyzing therapeutic antibodies. We compared the global gene expression profiles of spheroids and monolayers and identified genes specific to the 3-D biological structure of mesothelioma. An update on generation of human single-domain antibodies for cancer therapy will also be discussed.

2:30 Technology Showcase (Sponsorship Opportunities Available)

3D CELLULAR MODELS FOR DRUG AND TARGET SCREENING

This showcase provides an opportunity for sponsoring companies to showcase their new and emerging 3D cell models and technologies for the next generation of drug and target phenotypic screening.

2:30 High-Throughput Compatible Co-Spheroid Model Analyzing Compound Effects on Both Tumor and Stroma Cells

Sponsored by

Jan E. Ehlert, Ph.D., Head, Cellular Drug Discovery, ProQinase GmbHA spheroid-based co-culture system for the simultaneous analysis of compound effects on the proliferation of tumor as well as of stroma cells was established. The modular HTS-compatible system reveals results reflecting cell-specific drug susceptibility and cell/cell interactions.

2:50 Showcase #23:10 Showcase #3

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing

HIGH-CONTENT ANALYSIS OF TUMOR SPHEROID MODELS4:25 Chairperson’s Remarks

David Nolte, Ph.D., Professor, Physics, Purdue University; President, Animated Dynamics, Inc.

4:30 Drug Discovery and Development of Novel Anticancer Agents: Applications of Novel 3D Multicellular Tumor Spheroid ModelsDaniel V. LaBarbera, Ph.D., Assistant Professor, Drug Discovery and Medicinal Chemistry, The Skaggs School of Pharmacy and Pharmaceutical Sciences, The University of ColoradoAberrant regulation of epithelial-mesenchymal transition (EMT) is a driving force in the most prominent human diseases. In particular, EMT driven tumor progression promotes the expansion of cancer stem cells, drug resistance, and the mesenchymal phenotype, which is invasive with a high metastatic potential. Therefore, one therapeutic strategy to prevent metastatic dissemination is to develop small molecule drugs that can revert the mesenchymal phenotype to the more benign epithelial state. Using novel 3D multicellular tumor spheroid (MCTS) models of EMT, suitable for high-throughput and high-content screening (HTS/HCS), we have identified lead compounds that block TCF-transcription, which regulates the mesenchymal phenotype in colorectal cancer.

4:55 Novel Stromal Targets that Support Tumor Spheroid FormationShane R. Horman, Ph.D., Research Investigator, Advanced Assay Group, Genomics Institute of the Novartis Research FoundationThe stroma of solid organ tumors influences all phases of tumor progression indicating that environment may be dominant to the genetics of cancer cells. To expand these concepts to early stage drug discovery we have scrutinized the interactions between colon stroma and colorectal carcinoma (CRC) cells in a high content co-culture 3D spheroid screen. Subsequently we were able to identify novel fibroblast genes that, when depleted, abrogate CRC spheroid formation revealing an extended chemotherapeutic space by which to target tumors.

5:20 Developing Biodynamic Screening Assays for 3D Live-Tissue ModelsDavid Nolte, Ph.D., Professor, Physics, Purdue University; President, Animated Dynamics, Inc.Biodynamic screening performs three-dimensional functional imaging of living tissue by measuring drug-induced changes in intracellular dynamics. It is compatible with many 3D tissue formats, including tumor spheroids grown in bioreactors or in multiwell plates, as well as tissue biopsies and other organotypic models. Dynamics-based phenotypic profiling of tissues provides a new type of high-content screening. This talk presents 3D assays being developed for chemosensitivity and resistance, proliferation and toxicity screening.

5:45 Close of Day5:45 Short Course Registration

RECOMMENDED DINNER SHORT COURSE*6:00-9:00 (SC5) Expert ThinkTank: How to Meet the Need for Physiologically-Relevant Assays?*Separate registration required. See page 3 for details.

FASTCongress.com 15

Hotel & Travel Information Conference Hotel:Hyatt Boston Harbor Hotel101 Harborside DriveBoston, MA 02128Phone: 617-568-1234Website: www.bostonharbor.hyatt.com

Discounted Room Rate: $187 s/dDiscounted Cut-off Date: October 17, 2014Please visit www.fastcongress.com or call the hotel directly to reserve your sleeping accommodations. You will need to identify yourself as a Cambridge Healthtech Institute conference attendee to receive the discounted room rate with the host hotel. Reservations made after the cut-off date or after the group room block has been filled (whichever comes first) will be accepted at the discretion of the hotel. Rooms are limited, so please book early.

Why Stay at the Hyatt Boston Harbor Hotel Conveniently located near Logan airport, the Hyatt Boston Harbor Hotel boast beautiful views of Boston Harbor. Besides easy location, elegant guest rooms, and discounted room rates, all guests will have access to complimentary wireless internet.We understand that you have many choices when making your travel arrangements. Please understand that reserving your room in the CHI

room block at the conference hotel allows you to take full advantage of the conference sessions, events and networking opportunities, and ensures that our staff will be available to help should you have any issues with your accommodations.

Flight Discounts:Special discounts have been established with American Airlines for this conference.• Call American Airlines 1-800-433-1790 and use Conference code

23H4BR.• Go to www.aa.com/group and enter Conference code

23H4BR in promotion discount box.• Contact our dedicated travel agent, Rona Meizler at 1-617-559-3735 or

rona.meizler@protravelinc.com

Car Rental Discounts:Special rental discounts have been established with Hertz for this conference.• Call Hertz 1-800-654-3131 and use our Hertz Convention Number (CV):

04KL0005 • Go to www.hertz.com and use our Hertz Convention Number (CV):

04KL0005

WEDNESDAY, NOVEMBER 197:30 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

ENGINEERING COMPLEX 3D MODELS OF TUMOR MICROENVIRONMENT FOR DRUG SCREENING AND

FUNCTIONAL ANALYSIS8:00 Chairperson’s RemarksMary C. Farach-Carson, Ph.D., Rice University

8:10 Targeted Electric Field Therapy Development in 3D Models of the Heterogeneous Glioma MicroenvironmentScott S. Verbridge, Ph.D., Assistant Professor, School of Biomedical Engineering and Sciences, Virginia Tech – Wake Forest University3D tissue models that incorporate the physico-chemo-cellular heterogeneities of human tumors are a valuable tool for the development of treatments targeted against the cells that resist traditional therapies. We will discuss our recent work in targeting the physical properties of therapy-resistant brain cancer cells, leveraging 3D models to analyze the impact of cell type and mechanical microenvironment on cellular response to high frequency electric fields.

8:35 Targeting Physical and Stromal Determinants of Tumor Heterogeneity in Bioengineered 3D ModelsImran Rizvi, Ph.D., Instructor, Medicine and Dermatology, Harvard Medical School; Associate Bioengineer, Brigham and Women’s Hospital; Assistant, Biomedical Engineering, Wellman Center for Photomedicine, Massachusetts General HospitalThe biological characteristics and treatment response of cancers is influenced by an array of factors including flow-induced shear stress, stromal partners, and matrix composition, which play deterministic roles in the fate of disseminated tumours. Research platforms that integrate these cues are critically needed to identify mechanism-based combinations. Current findings will be presented on the impact of flow and stromal partners, including tumor endothelial cells, on the biological characteristics of 3D co-cultures, and their susceptibility to conventional and emerging therapies.

9:00 3D Hydrogel Co-Culture Systems for Growing Patient-Derived Xenografts: Use in Selective Drug ScreeningMary C. Farach-Carson, Ph.D., Ralph and Dorothy Looney Professor, Biochemistry and Cell Biology; Scientific Director, BioScience Research Collaborative, Rice UniversityBuilding on success culturing metastatic prostate cancer (PCa) cell lines using 3D HA-based hydrogels, we now can culture ‘never in 2D’ patient-derived xenograft (PDX) tumors alone or with other cells from the tumor microenvironment. Hydrogel-encapsulated PDX tumoroids retain viability over two weeks, proliferate and express androgen receptor, providing a valuable new platform for drug discovery and screening. We now aim to eliminate the ‘middle mouse’– a leap towards personalized medicine.

9:25 Human Stroma-Derived Extracellular Matrices: 3D ECM Physiological SystemsEdna Cukierman, Ph.D., Associate Professor, Cancer Biology, Fox Chase Cancer Center

The talk will describe desmoplasia (i.e., cancer-associated) and fibrosis in vivo-like 3D ECM models. It will highlight the system’s physiologic and pathologic relevance. The seminar will illustrate target validation, phenotype assessment, functional analysis and drug efficacy uses. Assorted tumor-associated microenvironments will showcase tissue patterning, multi-spectra acquisitions and digital imaging analyses together with classic cell biology and biochemistry approaches. Finally, the use of well-annotated human pathological samples will establish clinical applicability.

9:50 Coffee Break in the Exhibit Hall with Poster Viewing

ENGINEERING IN VITRO MODELS OF CANCER METASTASIS10:45 Chairperson’s RemarksAlan H. Wells, M.D., D.M.Sc., University of Pittsburgh

10:50 In vitro Models for Metastatic DiseaseRoger D. Kamm, Ph.D., Cecil and Ida Green Distinguished Professor, Biological and Mechanical Engineering, MIT

11:15 Monitoring Extravascular Migratory Metastasis of Angiotropic Cancer Cells Using a 3D in vitro Co-Culture SystemClaire Lugassy, M.D., Research Associate Professor, Pathology and Lab Medicine, UCLA School of Medicine; Member, Jonsson Comprehensive Cancer CenterDuring extravascular migratory metastasis (EVMM), angiotropic tumor cells migrate along the abluminal vascular surfaces without intravasation (pericytic-mimicry) and may spread to nearby or more distant sites. Our recent publication in Nature confirmed again the importance of this underexplored metastatic pathway. We have developed a fluorescence-based 3D co-culture model to monitor in real time single tumor cell migration/EVMM in a vascular microenvironment. This assay can be adapted for anticancer drug screening.

»KEYNOTE PRESENTATION11:40 An All-Human Microphysiologic Liver System for Carcinoma MetastasisAlan H. Wells, M.D., D.M.Sc., Vice Chair and Thomas J. Gill III Professor, Pathology, University of PittsburghMetastases kill patients, but disseminated cancers are resistant to therapies. The tumor biological events behind this are unknown due to lack of relevant model systems. Further, humans metabolize agents and present toxicities uniquely, hampering drug development. We have developed an all-human microphysiological system of the liver to study both tumor behavior in the common metastatic site, and drug metabolism/efficacy in the main metabolizing organ.

12:05 Using Block Cell Printing to Develop Single Cell Arrays for Drug ScreeningLidong Qin, Ph.D., Associate Member, Nanomedicine, Methodist Hospital Research Institute; Assistant Professor, Cell and Developmental Biology, Weill Cornell Medical College

12:30 pm Close of Physiologically-Relevant Cellular Tumor Models Conference

ADDITIONAL REGISTRATION DETAILSEach registration includes all 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 http://www.healthtech.com/regdetailsVideo and or audio recording of any kind is prohibited onsite at all CHI events.

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Pricing and Registration InformationNOVEMBER 17-18 NOVEMBER 18-19

Phenotypic Drug Discovery - Part I Phenotypic Drug Discovery - Part II

Engineering Functional 3D Models Screening and Functional Analysis of 3D Models

Organotypic Culture Models for Toxicology Physiologically-Relevant Cellular Tumor Models

CONGRESS PRICING – BEST VALUE!(Includes access to 2 conferences, excludes short courses)

Early Registration Discount until August 22, 2014 $2499 $1099Advance Registration Discount until October 10, 2014 $2699 $1199

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SINGLE CONFERENCE PRICING (Includes access to 1 conference, excludes short courses)

Early Registration Discount until August 22, 2014 $1399 $649Advance Registration Discount until October 10, 2014 $1599 $729Registrations after October 10, 2014 and on-site $1799 $799

DINNER SHORT COURSE PRICING(Includes access to short courses only. Add a short course to your conference registration and save $100.)

Single Short Course $699 $399Two Short Courses $999 $699Three Short Courses $1299 $899Add Short Course(s) and Save $100 -$100 -$100

Sunday Evening, November 16 6:00-9:00pm

Monday Evening, November 17 6:30-9:30pm

Tuesday Evening, November 18 6:00-9:00pm

(SC1) Introduction to High-Content Phenotypic Screening

(SC3) Stem Cell Models for Drug Discovery (SC5) Expert ThinkTank: How to Meet the Need for Physiologically-Relevant Assays?

(SC2) Exploring 3D Printing, Bioinks and Scaffolds

(SC4) Engineering Microfluidic Cell Culture Chips

CONFERENCE DISCOUNTS

Drug Safety Executive Council (DSEC)- Discount ($50 off) Members of the DSEC community will receive a $50 discount off the conference registration. Our records must indicate you are a memberPoster Submission- Discount ($50 off)Poster abstracts are due by October, 10, 2014. 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 jring@healthtech.com. *CHI reserves the right to publish your poster title and abstract in various marketing materials and products.

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