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 Third 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.
Final Agenda
Tuesday, June 19
7:30 am Registration Open (America Foyer) and Morning Coffee (Foyer)
8:15 Chairperson’s Opening Remarks
Peter Reinhardt, PhD, Head, Cell Programming and Transduction, Technology Core,
Neuroscience Discovery, AbbVie
8:20 Application of Disease-Specific iPS Cells to Increase the Success Rate of Drug Discovery
Gabriele Proetzel, PhD, Director, Regenerative Medicine, Takeda Pharmaceuticals, Inc.
With the recent advances in human iPSC technologies their utility in drug development has become increasingly evident. Patient-derived iPSC assays have produced valuable data in phenotypic screens and target validation. We will discuss examples and
how these impact the drug development process. I will describe how academic partnerships can accelerate such programs as exemplified by our collaboration with University of Kyoto, T-CiRA.
8:50 Strategies to Generate hiPSC-Derived Neural Cells for Robust in vitro Disease Modeling
Peter Reinhardt, PhD, Head, Cell Programming and Transduction, Technology Core, Neuroscience Discovery,
AbbVie
The human induced pluripotent stem cell (hiPSC) technology promises to revolutionize the discovery of drugs and treatments against neurodegenerative diseases. However, differentiation protocols into affected neural cells are often not suited for the
generation of large in vitro models. We will discuss several examples of how existing and novel protocols for the differentiation of hiPSCs into disease-affected neurons can be transformed into scalable and robust
assays fit for purpose.
9:20 iPSC-Based Disease Modeling to Advance Diabetes Drug Discovery
Melissa Thomas, MD, PhD, Medical Fellow, Diabetes and Complications, Eli Lilly and Company
We can generate β-like pancreatic cells that are fully functional as proven by either in vitro or in vivo studies. This novel proof-of-concept stem cell technology brings new
expectations on applying stem cell therapy for diabetes mellitus in clinical settings.
9:50 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)
10:35 Single Cell Models of Human Cardiac Development and Disease
Ibrahim Domian, MD, PhD, Assistant Physician, Massachusetts General Hospital, Assistant Professor of Medicine,
Harvard Medical School
Human Pluripotent Stem Cell-Derived Cardiomyocytes (hPSC-CMs) have been proposed as a robust cell source for human disease modeling and drug discovery. However, hPSC-CMs cultured in vitro are highly heterogeneous
in lineage commitment and metabolic maturation limiting their application. To address this, we have developed novel strategies to simultaneously assess gene expression and cell physiology in a multiplexed fashion at single living cell resolution
for the study of metabolic cardiovascular disease.
11:05 KEYNOTE PRESENTATION: From Stem Cells to Kidney Organoids to Disease Modeling
Joseph Bonventre, MD, PhD, Chief of the Renal Unit, Director of the Bioengineering Division, Brigham and Women’s Hospital
This talk will describe current protocols for generation of kidney organoids from pluripotent embryonic stem cells and induced pluripotent stem cells (iPSCs), describe the use of these organoids for disease modeling, and describe initiatives to develop
innovative approaches to replacement of renal function in humans.
11:35 Human iPSC-Derived Cardiac and Neural Systems and Novel Tools to Drive Preclinical Development
Stefan Braam, PhD, CEO, Ncardia
Drug development is witnessing a shift from conventional target-based drug discovery to a more phenotypic approach, which is enabled by the development of more physiological cellular tools. Here we provide several case studies that utilize human induced
pluripotent stem cell-derived cardiomyocytes, neurons, and novel tools within this space. These systems offer a flexible, highly translational and typically more predictive cellular environment than immortalized cell lines or even primary rodent
models.
12:05 Enjoy Lunch on Your Own
1:15 Chairperson’s Remarks
Ibrahim Domian, MD, PhD, Assistant Physician, Massachusetts General Hospital, Assistant Professor of Medicine, Harvard Medical School
1:20 Leveraging Stem Cell Technology to Fuel Drug Discovery for Neurodegenerative Diseases
Carlo Cusulin, PhD, Senior Scientist, Disease Relevant Cellular Assays, Chemical Biology, F. Hoffmann-La Roche
Drug discovery for neurodegenerative diseases presents several challenges because of the complexity of these disorders and the scarcity of reliable and translatable models. iPS technology offers the possibility to produce the relevant cell types (i.e.,
neurons, microglia, astrocytes) and introduce disease stimuli to obtain an in vitro system amenable for screening. We focused on generating models of Alzheimer’s disease, starting from patient-derived iPSCs
and assessing the effect of disease-modifying compounds.
1:50 iPSC Derived Neurons and Microglia for in vitro Pharmacology
Johannes Grosse, PhD, Director, Neuroscience Drug Discovery/Alliances, Takeda
The discrepancy between the massive private and academic investments in drug discovery for neurological and psychiatric diseases and the small and still declining number in novel drug approvals is a clear indicator for the unique challenges of
the field. Those have been identified at all phases of drug discovery from target validation and hypothesis via pre-clinical models for pharmacological tests to the design of clinical trials, use of biomarkers and regulatory affairs.
2:20 Advanced Physiologically Relevant hiPSC-Based Platforms for Drug Discovery
Fabian Zanella, Director, Research & Development, StemoniX
We present human induced pluripotent stem cell (hiPSC)-based platforms which were structurally engineered with greater physiological relevance aimed to elevate performance in drug discovery applications. microBrain® 3D comprises cortical
neural spheroids that feature high functionality with robust spontaneous activity and expected responses to established neuromodulators. microHeart® allows cardiomyocytes to adopt cell geometries and intercellular organization that
resemble native heart tissue, translating into differential pharmacological response to known cardioactive compounds.
2:50 Refreshment Break in the Exhibit Hall with Poster Viewing (America Ballroom)
3:30 Modeling Good Behavior: Is it Time to Raise the Bar on Pluripotent Stem Cell Derived Screening?
Sandra Engle, PhD, Associate Director, Translational Cellular Sciences, Stem Cells & Genomic Engineering,
Biogen
Ten years after its introduction, iPSC technology has matured. We can now better maintain pluripotency and differentiate cells to desired phenotypes with a reproducibility and scale that makes them amenable to larger scale screening efforts.
As iPSC-derived cells become a routine cell source for screening, we need to carefully consider how to use these cells to produce meaningful results. This talk will explore the current and future state of high through-put screening using
iPSC-derived neural cells.
4:00 All-Optical Electrophysiology for Neuroscience Drug Discovery
Graham Dempsey, PhD, Vice President, Research and Development, Q-State Biosciences
Human induced pluripotent stem (iPS) cell-based models have become a powerful approach to disease phenotyping for drug discovery applications. We have created an optogenetic platform called Optopatch that rapidly and robustly characterizes
the electrophysiological response of iPS cell-derived neurons. Our approach provides an information-rich readout of pharmacological changes in both intrinsic neuronal excitability and synaptic transmission with single-cell precision and
dramatically improved throughput.
4:30 PANEL DISCUSSION: iPSC-Based Neurodegenerative Disease Modeling
Moderator: Johannes Grosse, PhD, Director, Neuroscience Drug Discovery/Alliances, Takeda
Human neurodegenerative disorders are among the most difficult to study. This panel will discuss existing and future models for major neurodegenerative diseases.
- How do we establish that phenotypes “in a dish” are relevant to the patient’s disease?
- Does the relative immaturity of neurons in the dish matter and, if so, what do we do about it?
- What are the major technical barriers to high-throughput screening of iPSc-derived neuronal models?
- Does the technology circumvent the need for rodent preclinical neurodegenerative disease models?
Panelist: Carlo Cusulin, PhD, Senior Scientist, Disease Relevant Cellular Assays, Chemical Biology, F. Hoffmann-La Roche
Chee Yeun Chung, PhD, Scientific Co-Founder and Associate Director, Discovery Biology, Yumanity Therapeutics
Sandra Engle, PhD, Associate Director, Translational Cellular Sciences, Stem Cells & Genomic Engineering, Biogen
5:00 Find Your Table and Meet Your Moderator
5:05 Interactive Breakout Discussion Groups
This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of
ideas and active networking.
Modeling Neurodegenerative Disorders for Drug Discovery and Development
Bilada Bilican, PhD, Investigator II, Neuroscience, Novartis Institutes for BioMedical Research
(NIBR)
- In vitro correlates of complex neurodegenerative diseases.
- How to model apparently sporadic neurodegenerative disorders
- Advanced cellular models - how to address cell-autonomous vs. non-cell autonomous mechanisms of neurodegeneration
- Phenotype- vs. target-based drug screening
Infrastructure and Strategy for iPS Cell Based Drug Discovery
Gabriele Proetzel, PhD, Director, Regenerative Medicine, Takeda Pharmaceuticals, Inc.
Chee Yeun Chung, PhD, Scientific Co-Founder and Associate Director, Discovery Biology, Yumanity Therapeutics
- Technology advances
- Phenotypic screenings applications
- Target validation studies
5:45 Reception in the Exhibit Hall with Poster Viewing (America Ballroom)
7:00 Close of Day
Wednesday, June 20
7:45 am Registration Open (America Foyer) and Morning Coffee (Foyer)
8:25 Chairperson’s Remarks
Chee Yeun Chung, PhD, Scientific Co-Founder and Associate Director, Discovery Biology, Yumanity Therapeutics
8:30 Building a Robust Stem Cell-Based Discovery Platform for Neurodegenerative Diseases
Chee Yeun Chung, PhD, Scientific Co-Founder and Associate Director, Discovery Biology,
Yumanity Therapeutics
Phenotypic screening in neurons and glia derived from patients is now conceivable through unprecedented developments in reprogramming, transdifferentiation, and genome editing. We outline progress in this nascent field, but also consider
the formidable hurdles to identifying robust, disease-relevant and screenable cellular phenotypes in patient-derived cells. We illustrate how analysis in the simple baker’s yeast cell Saccharaomyces cerevisiae is driving
discovery in patient-derived neurons, and how approaches in this model organism can establish a paradigm to guide the development of stem cell-based phenotypic screens.
9:00 Functionalization of Schizophrenia GWAS Variants by High-Throughput Differentiation of Human Induced Pluripotent Stem Cells
Bilada Bilican, PhD, Investigator II, Neuroscience, Novartis Institutes for BioMedical
Research (NIBR)
Schizophrenia is a complex multifactorial and polygenic disorder, with both rare and common genetic variants contributing to disease risk. Genome-wide association studies (GWAS) have highlighted a large number of genetic variants with
potential disease association, but validation and prioritization of risk genes remains a challenge.
9:30 Developing Relevant In Vitro CNS Models for Drug Discovery
Daniel Haag, PhD, CSO, NeuCyte, Inc.
NeuCyte Inc. is a biotechnology company focusing on early phases of CNS drug discovery. Based on our SynFireTM technology, we have developed a proprietary human neural in vitro platform for
complex electrophysiological and morphological readouts suited for target identification and validation, efficacy testing and neurotoxicity assessment. Using patient-derived and genetically engineered defined neural cell types,
NeuCyte builds unique cell-based assays for modelling neurological and neurodegenerative disorders.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)
10:45 A 3D Culture Model of Alzheimer’s Disease: Towards a Cure-in-a-Dish?
Doo Yeon Kim, PhD, Assistant Professor of Neurology, Genetics and Aging Research Unit, Massachusetts
General Hospital / Harvard Medical School
Recently, we developed a novel 3D human neural culture model of Alzheimer’s disease (AD) that recapitulates key pathological markers of AD. In this presentation, I will show our recent progress including 1) improved 3D culture
models based on single-clonal hNPCs and microfluidic devices, 2) mechanistic studies to dissect pathogenic cascades that lead to NFT and neuronal death, and 3) our efforts to optimize 3D culture models for mid-throughput AD drug
screening against FDA-approved drugs.
11:15 Identification of Axon Growth Promoting Small Molecules Using a High Throughput Phenotypic Assay Exploiting HiPSC Derived Human Motor and Cortical Neurons
Bhagat Singh, PhD, Research Fellow, Neurobiology, Clifford Woolf’s Lab, Boston Children’s
Hospital, Harvard Medical School
We have generated standardized protocols to differentiate motor and cortical neurons from hiPSCs and also have developed a robust, sensitive and reproducible phenotypic neurite outgrowth assay (Z’>0.5) that recapitulates CNS
specific growth phenotypes in vitro. This provides us with a means to screen for regeneration-promoting compounds in a high throughput mode.
11:45 Session Break
11:50 Bridging Luncheon Presentation: Nuclear Imaging of Neuroinflammation in Rodent Models of Neurodegenerative Diseases
Tuulia Huhtala, PhD, Head, Biomarkers and in vitro Biology, Discovery, Charles River
Activation of the mitochondrial translocator protein (TSPO) is linked to neuroinflammation, and TSPO ligands can be used for in vivo PET or SPECT imaging. In the current studies, we utilized these
ligands to assess the extent of neuroinflammation after lipopolysaccharide (LPS) infusion, following induction of multiple sclerosis (MS) and neuropathic pain.
12:20 pm Dessert and Coffee Break in the Exhibit Hall with Poster Viewing
1:00 PLENARY KEYNOTE SESSION
Essex South
Partnering for Sustainable Funding
The panel is designed to discuss partnering between various stake holders such as drug discovery startups, VC firms, large pharmaceutical companies and academic labs in order to advance new target discovery and preclinical research.
VC companies, and pharma search & evaluation departments will be represented on the panel.
Jens Eckstein, PhD, President, SR One
Barbara K. Sosnowski, PhD, Vice President and Global Head, External R&D Innovation, Pharmatherapeutics and WRD External Partnerships, Pfizer, Inc.
Kevin Bitterman, PhD, Partner, Atlas Venture
Vivian Berlin, PhD, Director of Business Development, Life Sciences, Office of Technology Development, Harvard University
Ben Thorner, Senior Vice President and Head, MRL Business Development & Licensing, Merck
Plenary Technology Panel
Advancing Innovation in Drug Discovery and Translational Research
This year’s Plenary Technology Panel features a group of technical experts from life science technology and service companies, who share their perspectives on various trends and tools that will likely change the way in which
we traditionally approach preclinical drug discovery and development. Attendees will have an opportunity to ask questions and understand the impact of recent technical advances.
Moderator: Leigh Zawel, PhD, Managing Director, MPM Capital
Ashley Rae Kark, MBS, Director, Corporate Relations, Scientist.com
Stefan Braam, PhD, Technical Director, Ncardia
Mark Paris, PhD, Director, Translational Applications, Mitra Biotech
Edgard Wood, PhD, Senior Research Director, Discovery, Charles River
2:30 Refreshment Break in the Exhibit Hall with Poster Viewing (America Ballroom)
3:10 Close of Conference