Webinars

Hepatotoxicity is the leading cause for drug withdrawal from market and clinical trial.  Traditionally, liver safety risk assessment studies for humans have been conducted in animals during advanced preclinical or clinical phases of drug development.

However, the incredible costs associated with these late-stage drug failures have compelled the research community to screen for toxicity earlier in the drug discovery phase.

Furthermore, the ethical concerns and often poor predictivity around using animal models have encouraged researchers to validate human-based models for toxicity screening. The introduction of complex 3D liver spheroids this past decade has greatly improved predictive screening capabilities, as they can include several cell types and be maintained for several weeks.
Numerous endpoints are possible, but typically in high-throughput screens, only metabolic cell health (ATP) is measured.  The ‘omics’, such as genomics, proteomics, and metabolomics, have recently entered pharmaceutical research in both drug discovery and drug development, but few attempts in applying omics in high-throughput safety risk assessment have been attempted to date.  The omics approach is quite attractive, because in addition to its sensitivity, it allows for generation of a massive amount of data from a small quantity of cellular material.

Compared to traditional, low-density screening methods, this novel approach allows for multiple interconnected variables (lipids) to be measured simultaneously, providing a snapshot of the cellular status from the lipid perspective at the molecular level.

In this webinar, InSphero Scientific Ambassador Dr. Sue Grepper described a complex and high throughput 3D human liver model for assessing hepatotoxicity of therapeutics, along with a multitude of endpoints that can be assessed.  University of Perugia Professor Laura Goracci showcased an innovative lipidomic method that can be applied to these liver organoids to predict adverse drug effects in an early discovery phase.

A case study dataset highlighting 20 drugs belonging to five different therapeutic chemical classes was presented.

In this webinar, we covered:

• The advantages of using a 3D human liver model for identifying liver risk assessment
• A novel lipidomics approach for hepatotoxicity assessment at an early phase in drug discovery

Non-Alcoholic Steatohepatitis (NASH) is a serious and complicated disease with strong associations to other metabolic condition such as diabetes and obesity.

NASH begins with asymptomatic steatosis and can progress with subsequent liver inflammation and fibrosis leading to cirrhosis, liver failure, liver transplant and even hepatocellular carcinoma (HCC). Although there is an alarming percentage of the adult world population with at least early stages of NASH, there has not yet been a NASH drug approved for this complex disease, except the PPARα/γ agonist saroglitazar from Zydus.

The preclinical animal and cell culture models used to date have not accurately predicted drug efficacy effects once they reach the clinic, particularly with the fibrosis-associated endpoints.

In this webinar, InSphero Scientific Ambassador Dr. Sue Grepper focused on a novel human 3D NASH model, consisting of 4 different liver cell types relevant to this disease development. New findings were shared relating to compound modalities other than classic small molecules, as well as new quantitative fibrotic measurements achievable with this model.

PharmaNest CEO Dr. Mathieu Petitjean presented the FibroNest™ Digital Pathology AI platform for innovative phenotypic quantification of fibrosis based on histology liver slices of 3D NASH model using over 400 parameters relating to the fibrosis content, morphometry and architectural histological phenotypes. The fibrosis quantification in the 3D NASH model is extremely useful for better understanding the mechanism of action of anti-fibrotic compounds on collagen deposition.

The use of the FibroNest AI platforms allows to discover translational insights through similar quantifications and validations as performed for rodents and humans. This complex disease model and histological assay could be used as a translational drug discovery tool for prediction of efficacy and potency of anti-fibrotic compounds of in the clinic.

In this webinar, we covered:

• Modeling of key NASH hallmarks: steatosis, inflammation and fibrosis
• Scalable endpoints, including clinical biomarkers for drug efficacy testing
• Live demonstration of FibroNest™ Digital Pathology AI platform for phenotypic quantification of fibrosis based on histology tissue slices
• Efficacy testing of various modalities NASH compounds such as antibodies and small molecules

SBI2 High Content 2020 Educational Webinar

In vitro spheroid models are fast becoming the de facto standard for drug discovery applications, largely due to their human-like physiological and morphological characteristics, tissue-like cellular complexity, and long culture lifespan, which enables longitudinal studies that better reflect patient treatment plans in the clinic.

High content imaging and analysis (HCA) of 3D spheroid models can provide valuable information to help researchers untangle disease pathophysiology and assess novel therapies more effectively. Making the move from simple monolayer 2D cell models to dense 3D spheroids in HCI applications, however, requires 3D-optimized protocols, instrumentation, and resources.

In this webinar, we will discuss considerations for high content imaging and analysis of 3D spheroid disease models for drug discovery, share lessons we learned while in setting up and conducting proof-of-concept studies designed to test the full potential for high-resolution image-based analysis of 3D spheroid models and provide a working checklist for researchers and core services groups planning to exploit these technologies in their work.

You will learn:

• Core advantages of 3D models and 3D in vitro technology engineered for drug discovery applications, and the range of rich, physiologically relevant data you can extract from 3D disease models using HCA methods.
• Considerations when upgrading high content imaging from 2D to 3D, including fixation, staining, and clearing methods.
• Tips and tricks for image acquisition, including HCA instrumentation requirements, algorithm optimization, and our guidelines for automated confocal image settings and parameters.
• HCA data analysis methodologies for visualization of 3D image stacks, volumetric data, segmentation of 3D samples impacted by reduced light penetration, segmentation of individual cells to extract population data.
• How to harness the power of deep learning HCA capabilities to analyze and digitize highly complex imaging experiment data extracted from 3D models and live cell systems.

Webinar: The enabling technology underlying all InSphero 3D InSight™ drug discovery and safety platforms

Over the past decade, 3D spheroids have become the model of choice for many drug discovery applications due to their physiologically relevant morphological characteristics, cellular complexity, and longevity in culture.

Spheroids can now be engineered to mimic many human tissues and organs, ranging from simple tumor models derived from well-established cancer cell lines to complex triple-culture liver models produced from primary human donor cells. Increasingly, these 3D models have also been adapted for use in assay- and automation-ready plate formats, including 96- and 384-well plates, as well as emerging microfluidic systems that support organ networks.

In this webinar, InSphero Head of Technologies and Platforms Olivier Frey, PhD and Product Manager Frauke Greve, PhD, will give you an in-depth introduction to the 3D cell-culture technology underlying all InSphero platforms and services and share how our partners in academia and industry have helped us push the boundaries of what’s possible with 3D in vitro modeling today.
You will learn:

• How InSphero has engineered and optimized scalable, automation-friendly microplate technology for production and handling of complex multicellular 3D spheroid models that address the drug discovery needs of researchers, whether they want to use our models in-house for routine screening or engage InSphero as a discovery partner.
• The basics of biomicrofluidic devices that make plug-and-play organ-on-a-chip solutions more accessible and affordable for life science research teams
• Challenges of shipping live 3D cell cultures and the unique solution our team developed to ensure plates of microtissues always arrive upright and ready to assay
• Tips for choosing the most appropriate plates and 3D spheroid models for common biopharma applications, such as high throughput compound screening and high content imaging and analysis

A Strategic Approach for Applying 3D human in vitro Models and Methodologies to Bridge the Gap between In Vitro and In Vivo – The drug-induced liver injury (DILI) case

Despite ongoing investments in research, advances in technology, and improved knowledge and understanding of human disease modelling,  approximately 90% of new drugs entering clinical trials fail, largely due to safety issues in clinical phases or drug efficacy issues in patients. Why?

Because preclinical approaches that use in vivo animal models and in vitro cell models for discovery and development still do not reliably translate to patients.

In this webinar, InSphero CSO Prof. Armin Wolf will discuss how the research community gets “lost in translation” and share his strategy for bridging the divide between preclinical and clinical research to bring safe, effective drugs to market – and to patients in need of new therapeutics.

Prof. Armin Wolf will introduce a “causality assay” framework for evaluating drug-induced liver injury (DILI) with novel  3D in vitro models and methodologies, and explain how multicellular 3D human liver spheroids can be used for investigating a broad range of experimental conditions using a variety of analytical methods, from liver enzyme markers and histological techniques to the latest ‘omics technologies. He'll also walk you through several examples of successful applications of causality assays for the deconvolution of major DILI mechanisms – and offer his vision for the future of 3D in vitro tools for translational liver toxicology – and beyond.

You will learn:

• The challenges of drug discovery and translation (from in vitro and in vivo models to patients)
• The current gold standard: ATP-based DILI hazard identification
• Stepping beyond ATP: from hazard identification to risk assessment
• Impact of 3D spheroid models in drug development
• Future challenges and opportunities

Optimizing 3D In Vitro Technologies to Better Predict Patient Response to New Therapies

Non-alcoholic fatty liver disease (NAFLD) begins with excessive fat accumulation in the liver and can slowly progress in patients from asymptomatic steatosis (simple fatty liver) to non-alcoholic steatohepatitis (NASH, liver inflammation and fibrosis), to more advanced fibrosis and cirrhosis.

Effectively mimicking this chronic, multi-stage disease at the bench requires complex 3D in vitro liver models and assays that reflect human disease biology and response to treatments.

In this webinar, InSphero Senior Application Scientist Sue Grepper, PhD will provide an overview of the many different types of in vitro and in vivo models used for studying NAFLD and NASH. Then she’ll take you on a virtual tour of how the InSphero scientific team evaluates new drugs and therapies under development, using Gilead's Firsocostat, an ACC inhibitor currently in Phase II trials, as an example.

Sue will also share some of the latest results from our internal studies that show how NASH conditions affect regulation of lipid metabolism genes and pathways in our 3D in vitro models.

You will learn:

• The basics of human fatty liver disease and the challenges of modeling NAFLD and NASH in vitro
• The range of 3D liver models InSphero works with and how we choose the right model for each study based on research objectives and drug targets
• How to apply the latest 3D in vitro technologies (e.g., high-throughput screening, high content imaging, targeted mRNA sequencing, bioinformatics, etc.) to evaluate the effects of single and combination therapies using human 3D in vitro models that better predict patient response in the clinic
• Our scientific vision for the future of 3D in vitro modeling for NAFLD and NASH drug discovery