Cambridge Healthtech Institute’s 6th Annual

Disease Modeling

Developing, Validating, Scaling, and Automating Physiologically Relevant Disease Models

June 2-4, 2020


Inadequate representation of the human tissue environment during a preclinical screen can result in inaccurate predictions of a drug candidate’s effects. Thus, investigators are searching for preclinical models that closely resemble original tissue for predicting clinical outcome. 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 models that span all therapeutic areas. At Cambridge Healthtech Institute's 6th Annual Disease Modeling conference, we will discuss the next generation of models, as well as strategies to overcome common bottlenecks, such as standardization, scaling, and workflow integration.

Final Agenda

Recommended Short Course*

SC7: Intro to OOAC and Bioprinting for Disease Modeling

*Separate registration required.

Tuesday, June 2

10:00 am Main Conference Registration Open

MOVING TOWARDS A 3D PHYSIOLOGICALLY RELEVANT CELLULAR MODEL

11:15 Chairperson’s Remarks

Virneliz Fernandez Vega, Scientific Associate, Molecular Medicine, Scripps Research

11:20 Combining 3D Models and Functional Genomics in Preclinical Drug Development

Alejandro Amador, PhD, Scientific Leader, Platform Biology Automation, GSk

The current preclinical oncology drug discovery paradigm involves lengthy and costly optimization/lead discovery campaigns, often using cellular or in vivo tumor models with weak translational relevance that don’t closely resemble human solid tumors. I will highlight opportunities/challenges in implementing 3D solid tumor models. I will outline key components that should be considered when developing, validating, scaling, and automating 3D solid tumor models that are more physiologically relevant.

11:40 Adult Stem Cell Organoids: A Patient in the Lab

Robert Vries, PhD, CEO, Hubrecht Organoid Technology (HUB)

Key to the development of the HUB Organoid Technology was the discovery of adult stem cells by Hans Clevers. Provided with the appropriate growth factors, the adult stem cells form a polarized epithelium in which stem cells and their differentiated offspring maintain their natural hierarchy and function. In addition, the organoids are genetically stable during prolonged culture. Subsequently, we developed Organoid technology for most other epithelia. High-establishment efficiency means that we can use the Organoid Technology to generate disease models from virtually all patients.

12:00 pm Understanding Donor-to-Donor Variability in Healthy Human Gut-Derived Organoids

Linda Lieberman, PhD, Principal Scientist, Merck Exploratory Science Center

Primary organotypic cultures need to be robust and reproducible with limited donor-to-donor variability to advance discovery research toward complex functional tissue biology, yet donor-to-donor variability has not been characterized systematically for many human organoid systems. We established intestinal organoid cultures from adult stem cells of healthy donors and characterized inter- and intra-culture variability. We found that differentiation patterns were consistent among cultures and passages, producing all expected intestinal cell types.

12:20 In vitro Generation of Cancer-Associated Fibroblasts for 3D Culture Modeling of Immune-Excluded Tumors

Joanna Lee, PhD, Scientist, Genentech

12:55 Transition to Lunch

1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:30 Session Break

HOW TO SCALE UP 3D MODELS FOR HTS OR UHTS

2:00 Chairperson’s Remarks

Virneliz Fernandez Vega, Scientific Associate, Molecular Medicine, Scripps Research

2:05 3D Enteroid-Derived “Gut-in-a-Dish” Model for Developing Personalized Therapies for Chronic Inflammatory Diseases

Soumita Das, PhD, Associate Professor, Department of Pathology, Chief Scientific Director, HUMANOID Center of Research Excellence (CoRE), University of California, San Diego

We have developed a Gut-in-a-dish model from 3D organoids isolated from the intestinal specimens of healthy and diseased patients. This model consisting of epithelial cells, immune cells, and microbes could be utilized to investigate mechanisms for gastrointestinal inflammatory diseases, both oncogenic and non-oncogenic. A semi-HTP format of the model can be useful for the identification of new diagnostic and therapeutic targets, personalization of therapies through Phase “0” human trials, and much more.

2:35 3D Models of Brain Cancer for Precision Medicine Therapeutic Profiling

Virneliz Fernandez Vega, Scientific Associate, Molecular Medicine, Scripps Research

Our goal is to develop and validate a precision medicine therapeutic profiling technology by implementing rapid, cost-effective, physiologically relevant, functional 3D models of brain cancer for phenotypic evaluation of anti-cancer drugs. This combined with molecular pathology has been implemented into clinically pertinent information, which will improve the quality and speed of a physician’s decision-making for drug selection in treating cancer in a patient-specific manner.

3:05 Development of a Miniaturized 3D Organoid Culture Platform for Ultra-High-Throughput Screening (uHTS)

Yuhong Du, PhD, Associate Professor, Department of Pharmacology and Chemical Biology, Associate Director, Emory Chemical Biology Discovery Center (ECBDC), Emory University School of Medicine

“Organoids” with an extracellular matrix to support 3D architecture offer a new approach for drug discovery. However, it has been challenging for high-throughput screening (HTS)-based drug discovery due to technical difficulties. We have developed such a 3D organoid culture with an extracellular matrix in high-density, 1536-well plate for ultra-HTS (uHTS), and validated its application for large-scale primary compound screening. Our miniaturized platform provides an enabling technology to accelerate organoid-based drug discovery.

3:35 Methods and Media for the Differentiation of Human Intestinal Organoids and Organoid-Derived Monolayers

Martin Stahl, Scientist, R&D Intestinal, Stemcell Technologies Inc.

Organoid cultures have redefined the limits of biological data that can be obtained in vitro. Learn about how IntestiCult™ Organoid Differentiation Medium drives the differentiation of organoids and organoid-derived monolayer cultures into a more functional, differentiated epithelium that better recapitulates the cellular composition and function of the human intestinal epithelium.

3:50 CO-PRESENTATION: Advanced Peptide Hydrogels for 3D Models, Lab-on-Chip, and hiPSCs

Susan Sun, CTO, PepGel LLC

Todd Ringhouse, General Manager, PepGel LLC

PGmatrix 3D Models for cells, spheroids, and organoids from a variety of cells, stimulate the secretion of in vivo-like extracellular vesicles (exosomes). Biologically formed stem cell spheroids in PGmatrix demonstrate high pluripotency and differentiation potential at molecular levels. PGmatrix system is affordable, scalable, injectable, bioprintable, microfluidable and beyond.

4:05 Networking Refreshment Break and Transition to Keynote


PLENARY KEYNOTE SESSION

4:25 - 6:05 Driving Entrepreneurial Innovation to Accelerate Therapeutic Discoveries

The life sciences community has an unprecedented scientific arsenal to discovery, develop and implement treatments, cures and preventions that enhance human healthcare.

Moderator: Nadeem Sarwar, President, Eisai Center for Genetics Guided Dementia Discovery (G2D2), Eisai Inc.

Panelists: Anthony Philippakis, Chief Data Officer, Broad Institute; Venture Partner, GV

Barbara Sosnowski, Vice President and Global Head, Emerging Science & Innovation Leads, WWRDM, Pfizer

John Hallinan, Chief Business Officer, Massachusetts Biotechnology Council

6:05 Welcome Reception in the Exhibit Hall with Poster Viewing

7:10 Close of Day

Wednesday, June 3

7:30 am Registration Open and Morning Coffee

UTILIZING iPSC TO MODEL DISEASES AND EXPLORE TOMORROW’S THERAPEUTICs

8:10 Chairperson’s Remarks

Stefan Braam, PhD, CEO, Ncardia

8:15 FEATURED PRESENTATION: Generation, Validation & Application of iPSC Models in Early Discovery

Lisa Mohamet, PhD, Scientific Leader, Drug Design & Selection, GSK

This presentation will focus on the use of iPSC-derived platforms, complex in vitro models to improve disease relevance in phenotypic screening, and target engagement.

8:45 Using “Brains-in-a-Dish” to Investigate Developmental Features of Huntington Disease

Mahmoud Pouladi, PhD, Principal Investigator, Agency for Science, Technology and Research (A*STAR) and National University of Singapore (NUS)

Cerebral organoids grown from human embryonic and pluripotent stem cells can be used to perform detailed studies on brain development and to understand cellular mechanisms underlying Huntington’s disease. Details of these findings and other possible applications will be discussed.

9:15 Development of Patient-Derived iPSC Models and Phenotypic Assays for Early Drug Discovery in Neuroscience

Yoshiyuki Tsujihata, PhD, Director, Phenotypic Reverse Translation Lab, Neuroscience Drug Discovery Unit, Takeda Pharmaceutical Company Limited

Phenotypic assay/screening, with patient iPSC-derived models and quantitative image analysis, is an attractive strategy to develop innovative drugs in neurological disorders. Our strategy is to create simple and complex assay systems comprised of iPSC-derived neurons and glial cells and quantitatively capture pathological events, such as synapse plasticity and mitochondrial dysfunction. Those are being developed with a robustness that not only supports initial screening, but also downstream pharmacological and mechanistic evaluations.

9:45 Presentation to be Announced

 

10:00 Presentation to be Announced

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

BIOENGINEERED BLOOD-BRAIN BARRIER MODELS

11:00 Reconstruction of the Human Blood-Brain Barrier in vitro Reveals the Pathogenic Mechanisms of APOE4 in Cerebral Amyloid Angiopathy

Joel Blanchard, PhD, Postdoctoral Fellow, Picower Institute for Learning and Memory, MIT

Alzheimer’s disease leads to amyloid deposits along cerebral vasculature which impair the function of the blood-brain barrier (BBB) and accelerate cognitive degeneration. APOE4 is the strongest risk factor for cerebrovascular amyloid pathology (CAA) and Alzheimer’s disease (AD); however, the underlying pathogenic mechanisms are unknown. We developed an in vitro model of the human BBB that revealed the mechanisms through which APOE4 predisposes amyloid deposition, and uncovered new therapeutic opportunities for CAA and AD.

11:30 3D Alzheimer’s Disease (AD) Model for Studying the Blood-Brain Barrier Dysfunctions in Ad

Yoojin Shin, PhD, Postdoctoral Fellow, Mechanical Engineering, Roger Kamm’s Lab, MIT

We have developed a physiologically relevant three-dimensional (3D) Alzheimer’s disease (AD) model with a neurovascular unit (blood-brain barrier, BBB) including human neurons, astrocytes, pericytes, and brain endothelial cells in a microfluidic system. Using this model, we have investigated BBB dysfunction, such as the increase in permeability and abnormal angiogenesis in AD, and explored whether Aβ and/or toxic molecules disrupt normal BBB function.

12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Transition to Lunch

12:35 LUNCHEON PRESENTATION: Structural Maturation in the Development of hiPSC-Cardiomyocyte Models for Preclinical Safety, Efficacy, and Discovery

Nicholas Geisse, PhD, CSO, NanoSurface Biomedical

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 to address this gap typically trade off complexity with throughput, making them difficult to deploy in the modern development paradigm. NanoSurface technology leverages scalable engineering approaches in a cell-, assay-, and instrument-agnostic manner. It can be employed non-disruptively in nearly any workflow to enhance an assay’s predictive power.

1:05 Session Break


PLENARY KEYNOTE SESSION

1:45 - 3:15

Lgr5 Stem Cell-Based Organoids in Human Disease

Hans Clevers, MD, CSO, Director of Research, Princess Máxima Center for Pediatric Oncology, University Medical Center Utrecht; Principal Investigator, Hubrecht Institute for Developmental Biology and Stem Cell Research

Systematically Drugging Ras

Stephen Fesik, PhD, Professor of Biochemistry, Pharmacology, and

Chemistry, Orrin H. Ingram II Chair in Cancer Research, Vanderbilt

University School of Medicine

3:15 Refreshment Break in the Exhibit Hall with Poster Viewing

iPSC FOR TISSUE-CHIPS

4:00 Chairperson’s Remarks

Speaker to be Announced from Maxwell Biosystems

4:05 HiPSC-Based Disease Modeling and Taking iPSC Derivatives to the Clinic

Dhruv Sareen, PhD, Executive Director, Cedars-Sinai Biomanufacturing Center, Director, iPSC Core and Assistant Professor, Departments of Biomedical Sciences and BOG Regenerative Medicine Institute, Cedars-Sinai

This presentation will discuss modeling neurological, metabolic, and pancreatic diseases using iPSCs in different formats in vitro, including Tissue-Chips. Then it will discuss a pathway for taking iPSC-derived cells to the clinic describing processes used for cGMP manufacturing, including Cedars-Sinai’s new biomanufacturing center.

4:35 Neuromuscular Junction-on-a-Chip Model

Graham Marsh, PhD, Scientist II, BiogeN

Modeling the complex physiology of the human NMJ is essential to building our understanding of the underlying biology of diseases. We have developed a 3D co-culture model of the NMJ, including iPSC-derived motor neurons and skeletal muscle cells with physiological and translatable readouts that recapitulate a patient phenotype in vitro.

5:05 Find Your Table, Meet Your Moderator

5:10 Roundtable Breakout Discussions

TABLE: Organoids – Is It a Fad or an Enduring Technology?

Moderator: Angela Zhang, PhD, Product Manager, Epithelial Cell Biology, Research & Development, Stemcell Technologies

TABLE: Developing Organs-on-a-Chip/Microphysiological Systems for Drug Discovery

Moderator to be Announced

5:45 Reception in the Exhibit Hall with Poster Viewing

6:45 Close of Day

Thursday, June 4

8:00 am Registration Open and Morning Coffee


PLENARY KEYNOTE SESSION

8:30 - 9:40 Applications of Artificial Intelligence in Drug Discovery – Separating Hype from Utility

Patrick Walters, PhD, Senior Vice President, Computation, Relay Therapeutics

9:40 Coffee Break in the Exhibit Hall with Poster Viewing

BIOENGINEERED MODELS FOR DRUG DISCOVERY AND DEVELOPMENT

10:25 Chairperson’s Remarks

Roger Kamm, PhD, Cecil and Ida Green Distinguished Professor of Mechanical and Biological Engineering, Departments of Mechanical Engineering and Biological Engineering, Massachusetts Institute of Technology

10:30 KEYNOTE PRESENTATION: PhysioMimetics: Integration of Systems Biology with Organs-on-Chips for Drug Development

Linda Griffith, PhD, School of Engineering Professor of Teaching Innovation, Biological Engineering, and Mechanical Engineering, Massachusetts Institute of Technology

11:00 IQ MPS Consortium Update

Szczepan Baran, Head, Emerging Technologies, LAS, SO, Novartis

The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) is a technically-focused organization of pharmaceutical and biotechnology companies with a mission of advancing science and technology to augment the capability of member companies to develop transformational solutions that benefit patients, regulators, and the broader R&D community.

11:30 Biofabrication of 3D Tissues for Disease Modeling and Drug Screening

Marc Ferrer, PhD, Leader, Biomolecular Screening and Probe Development, Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health (NIH)

The NCATS 3D Tissue Bioprinting Laboratory is using biofabrication techniques together with quantitative assay technologies to produce architecturally and physiologically validated normal and diseased 3D tissue models in multi-well plate format to create an in-tissue assay platform for drug discovery and development that will be more clinically predicative than current in vitro cellular models. The presentation will describe the approach used at NCATS to create a portfolio of biofabricated 3D tissue models of the retina, skin, ometum and brain, as in tissue assay platforms for disease modeling, including age-related macular degeneration, atopic dermatitis and several cancers, and for pharmacological testing of toxicity and efficacy effects.

12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Transition to Lunch

12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:05 Dessert and Coffee Break in the Exhibit Hall with Poster Viewing

Drug safety and advanced models

2:00 Chairperson’s Remarks

Madhu Lal-Nag, PhD, Program Lead, Research Governance Council, Office of Translational Sciences, Center for Drug Evaluation & Research, U.S. Food and Drug Administration

2:05 Emerging Microphysiological Systems for Drug Safety Testing: A Regulatory Perspective

Madhu Lal-Nag, PhD, Program Lead, Research Governance Council, Office of Translational Sciences, Center for Drug Evaluation & Research, U.S. Food and Drug Administration

There is a great need to understand the synergy between the areas of translational and regulatory science research as they pertain to microphysiological systems and their application in evaluating safety and efficacy for therapeutic indications for different disease areas. My presentation will focus on identifying these areas of synergy and focus on the development of microphysiological systems that are a best fit for different applications.

2:35 Microphysiological Systems: Tissues on Chip for Safety, Toxicity, and Efficacy Tools in Precision Medicine

Danilo Tagle, PhD, Associate Director for Special Initiatives, National Center for Advancing Translational Sciences, National Institutes of Health

Microphysiological systems are bioengineered in vitro tools that mimic the 3D structure and function of human organ systems and have been developed to improve the predictive assessment of the safety and efficacy of promising therapeutics. The use of human-derived cells and tissues have increased the utility of tissue chips towards modeling diseases and for clinical trials on chips to inform human trial design. This presentation will focus on the latest advances in this promising technology.

3:05 Of Microtissues and Men: Applications of Advanced in vitro Systems in Toxicology

Matthew Wagoner, PhD, Director, Investigative Toxicology, Takeda Pharmaceutical

Advanced in vitro cell culture systems are transforming the way we design safer medicines. Here we share case studies of how neural, hepatic, and intestinal organoids are allowing us to more effectively detect and de-risk toxicity, while reducing a reliance on animal models.

3:35 Close of Conference

* The program is subject to change without notice, due to unforeseen reason.

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June 2-4

Accelerating Target Discovery

Expanding Chemical & Druggable Space

New Small Molecule Drug Targets

Emerging Indications and Modalities

Immuno-Oncology Advances

Disease Modeling

Preclinical Strategies, Models & Tools in Oncology

Advances in Drug Metabolism & Safety Testing

Immuno-Oncology Biomarkers

Clinical and Translational Biomarkers

AI for Drug Discovery and Development

June 3-4

Drug Discovery Technologies