Pioneering a new future of drug discovery rooted in 3D biology will empower researchers to personalize therapies, reduce a medicine’s time to market, and enhance quality of life for patients around the world.
BIOLOGY the PARADIGM SHIFT in NEXT-GEN DRUG DISCOVERY
What is the drug discovery paradigm?
A transition away from 2D cell cultures and animal models to...
more biologically-relevant 3D cell models and human systems
The revolutionary promise of 3D biology 12–18 years + $13B = 1 drug . . . . . . . . . . . . . . 5 Limitations of conventional cell models . . . 6 FDA Modernization Act 2.0 . . . . . . . . . . . . . . 7 Organoids Applications and research . . . . . . . . . . . . . . . 8 Organoidsinaction.....................9 The challenges with organoids. . . . . . . . . . . 10 Realizing a future of advanced drug discovery will require radical innovation To get there, we must . . . . . . . . . . . . . . . . . . 12 Organoid screening workflow . . . . . . . . . . . 13 Organoid Innovation Center . . . . . . . . . . . . . 14 Table of Contents
3D biology is an emerging field revolutionizing the way scientists screen new drugs and understand disease 3D cell models like organoids have a unique makeup that oer a step-change in predicting human responses to novel treatments. Their increased physiological relevance leads to more accurate indications of a therapeutic’s ecacy in the pre-clinical phase. This allows for a weeding out of toxic, ineective compounds to make space for those with healing power earlier in the drug discovery process. The REVOLUTIONARY PROMISE of 3D BIOLOGY
$13B DRUG 1 + =
90 percent of drug candidates fail during the first of three phases in clinical trials This alarming failure rate can be traced in part to reliance on 2D cell cultures or animal models that don’t closely mimic complex human biology. The results are inaccurate predictions of a drug’s potential and extended drug development timelines.
• Target identification/validation • Assay development • Lead generation DRUG DISCOVERY
5,000 - 10,000
• In vitro and in vivo toxicity • ADMET • PK/PD
• Phase I • Phase II • Phase III
Limitations of conventional cell models
Translatability and scale Though 2D cell models are easily scaled, they have low relative translatability – meaning they are not reliable indicators of a drug’s ecacy in humans. And while animal models have played a critical role in drug development studies, they are not always predictive of human response to drugs. The main reason for this discrepancy is a lack of translatability because animals and humans metabolize drugs dierently. Animal models are also dicult to humanely and cost-eectively scale.
Immortalized Cell Lines
Small Animal Models
Large Animal Models
FDA Modernization Act 2.0
Bipartisan bill signed into law allowing alternatives to animal testing for drug and biological product applications. This historic move toward animal-free testing refutes the Federal Food, Drug and Cosmetics Act (FFDCA) of 1938 mandating that all new drugs be tested in animals to protect patients from unknown toxicity. The U.S. Food and Drug Administration (FDA) can now consider alternatives for drug testing methods, like those rooted in 3D biology which oer higher predictive power and could limit the need for up to 156 million animals used in clinical testing today.
How scientists integrate organoids into their research Organoids are 3D cultures derived from stem cells or organ progenitor cells that recapitulate the structure and cellular complexity of human organs like the brain, heart, lung, intestine, and more. They naturally self-organize into clusters and dierentiate into cell types that represent in vivo tissue and some organ function. This greater complexity and sophistication allow researchers to facilitate next-generation drug discovery and better predict success in the clinic. Organoid application & research
Organoids in action
Case studies and expert insight
Because they so closely resemble their internal organ counterparts, organoids have proven to be an accurate model for studying human disease, screening drugs, and testing potential therapeutics. They’re also an especially useful tool for precision medicine. For example, patient derived organoids can be generated from individuals with specific ailments and used to better understand disease, develop drugs, and customize personalized therapies.
Resemble organ functionality
Multicellular and 3D
Models major tissue types
The challenges with organoids
More complex protocols are required to overcome barriers to 3D biology adoption
Standard protocol to produce robust and reproduciblle spheroids/organoids
Organoids may oer greater predictability and more
biologically-relevant data than 2D cell models, but their wider adoption remains limited. They can be dicult to grow in-house without the right protocols, technology, or know-how, and access to reliable o-the-shelf options are minimal. Associated technical hurdles and assay complexity lead to higher costs, lower throughput, and reproducibility hurdles.
Ability to do automated passaging
“Turn-key” system to grow, monitor, and screen organoids
stated that their biggest pain point was developing a standard protocol to produce robust and reproducible spheroids/organoids. 55% of researchers
Access to stable cell lines for growing 3D models
Software to track from single cell to 3D organoids and provide deep insights with AI
Shorter amount of time to grow 3D models
Ability to produce the # of organoids required for screening
Realizing a future of advanced drug discovery will require radical innovation
To get there, we must:
Exploit automation technologies to scale complex 3D biology research in a high throughput screening environment
Increase access to organoids pioneering a future where researchers are empowered to personalize therapies, improving global health
Commercialize fully-integrated screening solutions bringing end-to-end workflows together connecting cell line development with 3D biology
Maximize use of artificial intelligence to guide data-driven analysis and decision-making across the entire drug discovery process
Organoid screening workflow
Automated high-throughput screening solution
Monitoring organoid growth & development
Confocal imaging & 3D analysis
Developing 3D organoids
An end-to-end solution standardizes the organoid development process with cell culture, treatment, and incubation, through to imaging, analysis, and data processing, delivering consistent, unbiased, and biologically-relevant results at scale.
ImageXpress Confocal high content imaging system
AquaMax microplate washer
SpectraMax microplate readers/ SoftMax Pro Gxp software
ImageXpress Pico automated cell imager
AUTOMATED LAB COMPONENTS
Automation scheduling software
Automated liquid handler
Automated CO2 incubator
Organoid Innovation Center
Quickly adopt innovative, 3D biological methods and technologies for drug discovery The Organoid Innovation Center combines cutting-edge technologies with novel research methods to address key challenges of scaling complex biology assays. The collaborative space brings customers and researchers into the lab to test automated workflows for organoid culturing and screening, with guidance from in-house scientists.
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