Cambridge Healthtech Institute’s 6th Annual

Disease Modeling

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

September 16 - 17, 2020 ALL TIMES EDT

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.

Wednesday, September 16

MOVING TOWARDS A 3D PHYSIOLOGICALLY RELEVANT CELLULAR MODEL

9:30 am 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.

9:50 am

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.

Szilard Sajgo, PhD, Application Scientist, MaxWell Biosystems

Electrical activity of brain, retina or muscle organoids can now be easily characterized, label free, at single-cell resolution by using MaxWell Biosystems’ high-density microelectrode array (HD-MEA) technology. We will present HD-MEA results from human iPSC-derived organoids modeling different brain compartments and demonstrate the potential of the technology for drug testing.

10:30 am IQ MPS Consortium Update
Szczepan W. Baran, Head, Emerging Technologies, Novartis Institutes for Biomedical Research

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.

Panel Moderator:
Szilard Sajgo, PhD, Application Scientist, MaxWell Biosystems
Panelists:
Szczepan W. Baran, Head, Emerging Technologies, Novartis Institutes for Biomedical Research
Linda Lieberman, PhD, Principal Scientist, Merck Exploratory Science Center
Robert Vries, PhD, CEO, Hubrecht Organoid Technology (HUB)
11:10 am Coffee Break - View Our Virtual Exhibit Hall
11:25 am

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.

11:45 am 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.

Ji Wu, PhD, Vice President of Business Development and Operations, BD and Operations, NeuCyte

NeuCyte develops hiPSC-based in vitro systems for modeling of neurological diseases. The platform allows for efficient testing of drugs in a scalable environment of human neurophysiology early in the drug development process. We will share how NeuCyte applies it for modeling disorders such as epilepsy, Fragile X syndrome and more.

12:25 pm LIVE Q&A:

Session Wrap-Up Panel Discussion

Panel Moderator:
Ji Wu, PhD, VP Bus Dev, Bus Dev, Neucyte Inc
Panelists:
Joel Blanchard, PhD, Postdoctoral Fellow, Picower Institute for Learning and Memory, MIT
Virneliz Fernandez-Vega, Scientific Associate, Molecular Medicine, Scripps Research
12:45 pm Lunch Break - View Our Virtual Exhibit Hall

HOW TO SCALE UP 3D MODELS FOR HTS OR UHTS

1:15 pm 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.

1:35 pm

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.

Martin Stahl, PhD, Scientist, Research & Development, 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.

2:15 pm LIVE Q&A:

Session Wrap-Up Panel Discussion

Panel Moderator:
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)
Panelists:
Soumita Das, PhD, Associate Professor, Department of Pathology, Chief Scientific Director, HUMANOID Center of Research Excellence (CoRE), University of California, San Diego
Martin Stahl, PhD, Scientist, Research & Development, Stemcell Technologies, Inc
2:35 pm Refresh Break - View Our Virtual Exhibit Hall
3:00 pm Interactive Breakout Discussions - View Our Virtual Exhibit Hall

Join a breakout discussion group. These are informal, moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic. Discussion topics and moderators will be listed on the website.

Stefan Braam, CEO & CSO, Ncardia BV

- Where can iPSC based disease models be best applied in the drug discovery funnel?

- Are drug responses affected by the genetic background of iPSCs?

- What is needed for successful implementation of iPSC disease models in drug discovery?

- What are the benefits of using iPSCs for drug discovery?

3:35 pm Close of Day

Thursday, September 17

BIOENGINEERING MICROPHYSIOLOGICAL SYSTEMS

10:15 am KEYNOTE PRESENTATION: PhysioMimetics: Integration of Systems Biology with Organs-on-Chips for Drug Development
Linda Griffith, PhD, Professor, Biological Engineering & Teaching Innovation, Massachusetts Institute of Technology
10:35 am

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.

10:55 am 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.

Nicholas Geisse, PhD, Chief Science Officer, Curi Bio

iPSC-CM model systems have relatively immature phenotypes, critically limiting their ability to model human function. Here, we will present novel, high-throughput bioengineering methods to improve the maturity and predictivity of 2D and 3D iPSC-CM model systems that can be implemented in a cell-, instrument-, and assay-agnostic manner. 

11:35 am LIVE Q&A:

Session Wrap-Up Panel Discussion

Panel Moderator:
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
Panelists:
Linda Griffith, PhD, Professor, Biological Engineering & Teaching Innovation, Massachusetts Institute of Technology
Madhu Lal-Nag, PhD, Program Lead, Research Governance Council, Office of Translational Sciences, Center for Drug Evaluation & Research, U.S. Food and Drug Administration
Nicholas Geisse, PhD, Chief Science Officer, Curi Bio
Danilo Tagle, PhD, Associate Director for Special Initiatives, National Center for Advancing Translational Sciences, National Institutes of Health
11:55 am Coffee Break - View Our Virtual Exhibit Hall

PLENARY KEYNOTE PROGRAM

12:20 pm

PLENARY KEYNOTE: Tackling Undruggable Oncoproteins: Lessons from the VHL Tumor Suppressor Protein

William G. Kaelin, Jr., MD, 2019 Nobel Laureate; Professor, Medical Oncology, Dana-Farber Cancer Institute; Investigator, Howard Hughes Medical Institute; Co-Founder, Cedilla and Tango Therapeutics

VHL tumor suppressor protein (pVHL) inactivation is common in kidney cancer and upregulates the HIF2 transcription factor. PT2977/MK-6482 is an allosteric HIF2 inhibitor now in Phase 3 testing. Thalidomide-like drugs (IMiDs) bind to cereblon which, like pVHL, is the substrate-binding unit of a ubiquitin ligase. IMiDs redirect cereblon to destroy the myeloma oncoproteins, IKZF1 and IKZF3. We have developed new assays for identifying drugs that can destabilize oncoproteins of interest.

12:45 pm LIVE Q&A:

Plenary Keynote Discussion

Panel Moderator:
Stewart Fisher, PhD, CSO, C4 Therapeutics, Inc.
Panelist:
William G. Kaelin, Jr., MD, 2019 Nobel Laureate; Professor, Medical Oncology, Dana-Farber Cancer Institute; Investigator, Howard Hughes Medical Institute; Co-Founder, Cedilla and Tango Therapeutics
12:55 pm LIVE PANEL AND Q&A:

Plenary Keynote Discussion: De-Risking Early Drug Discovery

Panel Moderator:
Nadeem Sarwar, PhD, Founder & President, Eisai Center for Genetics Guided Dementia Discovery, Eisai, Inc.
  • Data Sciences
  • ​Novel Chemical Modalities
  • Investment and Partnering Models
  • COVID-19 Progress as Examples of Successful Partnerships
Panelists:
Anthony A. Philippakis, PhD, Chief Data Officer, Data Sciences & Data Engineering, Broad Institute; Venture Partner, GV
Stephen A. Hitchcock, PhD, Head, Research, Takeda Pharmaceuticals, Inc.
1:35 pm Lunch Break - View Our Virtual Exhibit Hall
2:05 pm Close of Disease Modeling Conference





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