Cambridge Healthtech Institute’s 4th Annual

iPS Cells for Disease Modeling and Drug Discovery

Pluripotent Stem Cells for Disease Research

June 19-20, 2019

With advances in reprogramming and differentiation technologies, as well as with the recent availability of gene editing approaches, we are finally able to create more complex and phenotypically accurate cellular models based on pluripotent cell technology. This opens new and exciting opportunities for pluripotent stem cell utilization in early discovery, preclinical and translational research. CNS diseases and disorders are currently the main therapeutic area of application with some impressive success stories resulted in clinical trials. Cambridge Healthtech Institute’s 4th Annual iPS Cells for Disease Modeling and Drug Discovery conference is designed to bring together experts and bench scientists working with pluripotent cells and end users of their services, researchers working on finding cures for specific diseases and disorders.

Wednesday, June 19

12:00 pm Registration Open

NanosurfaceBiomedical 12:00 Bridging Luncheon Presentation: Structural Maturation in the Development of hiPSC-Cardiomyocyte Models for Pre-clinical Safety, Efficacy, and Discovery

Geisse_NicholasNicholas Geissse, PhD, CSO, NanoSurface Biomedical

Smith_AlecAlec S.T. Smith, PhD, Acting Instructor, Bioengineering, University of Washington

hiPSC-CM maturation is sensitive to structural cues from the extracellular matrix (ECM). Failure to reproduce these signals in vitro can hamper experimental reproducibility and fidelity. Engineering approaches that address this gap typically trade off complexity with throughput, making them difficult to deploy in the modern drug development paradigm. The NanoSurface Car(ina)™ platform leverages ECM engineering approaches that are fully compatible with industry-standard instrumentation including HCI- and MEA-based assays, thereby improving their predictive power.

12:30 Transition to Plenary


2:20 Booth Crawl and Dessert Break in the Exhibit Hall with Poster Viewing

2:25 Meet the Plenary Keynotes

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3:05 Chairperson’s Remarks

Gabriele Proetzel, PhD, Director, Neuroscience Drug Discovery, Takeda Pharmaceuticals, Inc.

3:10 KEYNOTE PRESENTATION: iPSC-Based Drug Discovery Platform for Targeting Innate Immune Cell Responses

Christoph Patsch, PhD, Team Lead Stem Cell Assays, Disease Relevant Cell Models and Assays, Chemical Biology, Therapeutic Modalities, Roche Pharma Research and Early Development

The role of innate immune cells in health and disease, respectively their function in maintaining immune homeostasis and triggering inflammation makes them a prime target for therapeutic approaches. In order to explore novel therapeutic strategies to enhance immunoregulatory functions, we developed an iPSC-based cellular drug discovery platform. Here we will highlight the unique opportunities provided by an iPSC-based drug discovery platform for targeting innate immune cells.

3:40 Phenotypic Screening of Induced Pluripotent Stem Cell Derived Cardiomyocytes for Drug Discovery and Toxicity Screening

Bruyneel_ArneArne Bruyneel, PhD, Postdoctoral Fellow, Mark Mercola Lab, Cardiovascular Institute, Stanford University School of Medicine

Cardiac arrhythmia and myopathy is a major problem with cancer therapeutics, including newer small molecule kinase inhibitors, and frequently causes heart failure, morbidity and death. However, current in vitro models are unable to predict cardiotoxicity, or are not scalable to aid drug development. However, with recent progress in human stem cell biology, cardiac differentiation protocols, and high throughput screening, new tools are available to overcome this barrier to progress.


4:10 Disease Modeling Using Human iPSC-Derived Telencephalic Inhibitory Interneurons - A Couple of Case Studies

Yishan Sun, PhD, Investigator, Novartis Institutes for BioMedical Research (NIBR)

Human iPSC-derived neurons provide the foundation for phenotypic assays assessing genetic or pharmacological effects in a human neurobiological context. The onus is on assay developers to generate application-relevant neuronal cell types from iPSCs, which is not always straightforward, given the diversity of neuronal classes in the human brain and their developmental trajectories. Here we present two case studies to illustrate the use of iPSC-derived telencephalic GABAergic interneurons in neuropsychiatric research.

4:40 Rethinking the Translational – The Use of Highly Predictive hiPSC-Derived Models in Pre-Clinical Drug Development

Braam_StefanStefan Braam, CEO, Ncardia

Current drug development strategies are failing to increase the number of drugs reaching the market. One reason for low success rates is the lack of predictive models. Join our talk to learn how to implement a predictive and translational in vitro disease model, and assays for efficacy screening at any throughput.

5:10 4th of July Celebration in the Exhibit Hall with Poster Viewing

5:30 - 5:45 Speed Networking: Oncology

6:05 Close of Day

5:45 Dinner Short Course Registration

6:15 Dinner Short Course*

*Separate registration required.

Thursday, June 20

7:15 am Registration

7:15 Breakout Discussion Groups with Continental Breakfast

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8:10 Chairperson’s Remarks

Jeff Willy, PhD, Research Fellow, Discovery and Investigative Toxicology, Vertex

8:15 Levering iPSC to Understand Mechanism of Toxicity

willy_JeffJeff Willy, PhD, Research Fellow, Discovery and Investigative Toxicology, Vertex

The discovery of mammalian cardiac progenitor cells suggests that the heart consists of not only terminally differentiated beating cardiomyocytes, but also a population of self-renewing stem cells. We recently showed that iPSC cardiomyocytes can be utilized not only to de-risk compounds with potential for adverse cardiac events, but also to understand underlying mechanisms of cell-specific toxicities following xenobiotic stress, thus preventing differentiation and self-renewal of damaged cells.

8:45 Pluripotent Stem Cell-Derived Cardiac and Vascular Progenitor Cells for Tissue Regeneration 

Nutan Prasain, PhD, Associate Director, Cardiovascular Programs, Astellas Institute for Regenerative Medicine (AIRM)

This presentation will provide the review on recent discoveries in the derivation and characterization of cardiac and vascular progenitor cells from pluripotent stem cells, and discuss the therapeutic potential of these cells in cardiac and vascular tissue repair and regeneration.


9:15 Use of iPSC–Derived Hepatocytes to Identify Treatments for Liver Disease

Duncan_StephenStephen A. Duncan, PhD, Smartstate Chair in Regenerative Medicine, Professor and Chairman, Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina

MTDPS3 is a rare disease caused by mutations in the DGUOK gene, which is needed for mitochondrial DNA (mtDNA) replication and repair. Patients commonly die as children from liver failure primarily caused by unmet energy requirements. We modeled the disease using DGOUK deficient iPSC derived hepatocytes and performed a screen to identify drugs that can restore mitochondrial ATP production.

9:45 Industrial-Scale Generation of Human iPSC-Derived Hepatocytes for Liver-Disease and Drug Development Studies

Quinn_LizLiz Quinn, PhD, Associate Director, Stem Cell Marketing, Marketing, Takara Bio USA

Our optimized hepatocyte differentiation protocol and standardized workflow mimics embryonic development and allows for highly efficient differentiation of hPSCs through definitive endoderm into hepatocytes. We will describe the creation of large panels of industrial-scale hPSC-derived hepatocytes with specific genotypes and phenotypes and their utility for drug metabolism and disease modeling.

10:15 Coffee Break in the Exhibit Hall with Poster Viewing

10:45 Poster Winner Announced


11:00 KEYNOTE PRESENTATION: Modeling Human Disease Using Pluripotent Stem Cells

Lorenz Studer, MD, Director, Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center

One of the most intriguing applications of human pluripotent stem cells is the possibility of recreating a disease in a dish and to use such cell-based models for drug discovery. Our lab uses human iPS and ES cells for modeling both neurodevelopmental and neurodegenerative disorders. I will present new data on our efforts of modeling complex genetic disease using pluripotent stem cells and the development of multiplex culture systems.

11:30 Preclinical Challenges for Gene Therapy Approaches in Neuroscience

gabriele-proetzelGabriele Proetzel, PhD, Director, Neuroscience Drug Discovery, Takeda Pharmaceuticals, Inc.

Gene therapy has delivered encouraging results in the clinic, and with the first FDA approval for an AAV product is now becoming a reality. This presentation will provide an overview of the most recent advances of gene therapy for the treatment of neurological diseases. The discussion will focus on preclinical considerations for gene therapy including delivery, efficacy, biodistribution, animal models and safety.

12:00 pm Open Science Meets Stem Cells: A New Drug Discovery Approach for Neurodegenerative Disorders

durcan_ThomasThomas Durcan, PhD, Assistant Professor, Neurology and Neurosurgery, McGill University

Advances in stem cell technology have provided researchers with tools to generate human neurons and develop “first-of-their-kind” disease-relevant assays. However, it is imperative that we accelerate discoveries from the bench to the clinic and the Montreal Neurological Institute (MNI) and its partners are piloting an “Open Science” model. By removing the obstacles in distributing patient samples and assay results, our goal is to accelerate translational medical research.

Stemonix 12:30 NEW: Elevating Drug Discovery with Advanced Physiologically Relevant Human iPSC-Based Screening Platforms

Blake Anson, PhD, Director, Marketing, StemoniX

Structurally engineered human induced pluripotent stem cell (hiPSC)-based platforms enable greater physiological relevance, elevating performance in toxicity and discovery studies. StemoniX’s hiPSC-derived platforms comprise neural (microBrain) or cardiac (microHeart) cells constructed with appropriate inter- and intracellular organization promoting robust activity and expected responses to known cellular modulators.

1:00 Overcoming Challenges in CNS Drug Discovery through Developing Translatable iPSC-derived Cell-Based Assays

Davila_JonJonathan Davila, PhD, CEO, Co-Founder, NeuCyte Inc.

Using direct reprogramming of iPSCs to generate defined human neural tissue, NeuCyte developed cell-based assays with complex neuronal structure and function readouts for versatile pre-clinical applications. Focusing on electrophysiological measurements, we demonstrate the capability of this approach to identify adverse neuroactive effects, evaluate compound efficacy, and serve phenotypic drug discovery.

1:15 Enjoy Lunch on Your Own

1:35 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing

1:45 - 2:00 Speed Networking: Last Chance to Meet with Potential Partners and Collaborators!


2:20 Chairperson’s Remarks

Gary Gintant, PhD, Senior Research Fellow, AbbVie

2:25 The Evolving Roles of Evolving Human Stem Cell-Derived Cardiomyocyte Preparations in Cardiac Safety Evaluations

Gintant_GaryGary Gintant, PhD, Senior Research Fellow, AbbVie

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for preclinical cardiac safety testing. Recent applications focus on drug effects on cardiac electrophysiology, contractility, and structural toxicities, with further complexity provided by the growing number of hiPSC-CM preparations being developed that may also promote myocyte maturity. The evolving roles (both non-regulatory and regulatory) of these preparations will be reviewed, along with general considerations for their use in cardiac safety evaluations.

2:55 Pharmacogenomic Prediction of Drug-Induced Cardiotoxicity Using hiPSC-Derived Cardiomyocytes

Burridge_PaulPaul W. Burridge, PhD, Assistant Professor, Department of Pharmacology, Center for Pharmacogenomics, Northwestern University Feinberg School of Medicine

We have demonstrated that human induced pluripotent stem cell-derived cardiomyocytes successfully recapitulate a patient’s predisposition to chemotherapy-induced cardiotoxicity, confirming that there is a genomic basis for this phenomenon. Here we will discuss our recent work deciphering the pharmacogenomics behind this relationship, allowing the genomic prediction of which patients are likely to experience this side effect. Our efforts to discover new drugs to prevent doxorubicin-induced cardiotoxicity will also be reviewed.

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3:25 Exploring the Utility of iPSC-Derived 3D Cortical Spheroids in the Detection of CNS Toxicity

Qin Wang, PhD, Scientist, Drug Safety Research and Evaluation, Takeda

Drug-induced Central Nervous System (CNS) toxicity is a common safety attrition for project failure during discovery and development phases due low concordance rates between animal models and human, absence of clear biomarkers, and a lack of predictive assays. To address the challenge, we validated a high throughput human iPSC-derived 3D microBrain model with a diverse set of pharmaceuticals. We measured drug-induced changes in neuronal viability and Ca channel function. MicroBrain exposure and analyses were rooted in therapeutic exposure to predict clinical drug-induced seizures and/or neurodegeneration. We found that this high throughput model has very low false positive rate in the prediction of drug-induced neurotoxicity.

3:55 Linking Liver-on-a-Chip and Blood-Brain-Barrier-on-a-Chip for Toxicity Assessment

lelievre_sophieSophie Lelievre, DVM, PhD, LLM, Professor, Cancer Pharmacology, Purdue University College of Veterinary Medicine

One of the challenges to reproduce the function of tissues in vitro is the maintenance of differentiation. Essential aspects necessary for such endeavor involve good mechanical and chemical mimicry of the microenvironment. I will present examples of the management of the cellular microenvironment for liver and blood-brain-barrier tissue chips and discuss how on-a-chip devices may be linked for the integrated study of the toxicity of drugs and other molecules.

4:25 Close of Conference

Arrive early to attend Tuesday, June 18 - Wednesday, June 19

Chemical Biology and Target Validation