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 + $1 . 3B = 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 o er a step-change in predicting human responses to novel treatments. Their increased physiological relevance leads to more accurate indications of a therapeutic’s e cacy in the pre-clinical phase. This allows for a weeding out of toxic, ine ective compounds to make space for those with healing power earlier in the drug discovery process. The REVOLUTIONARY PROMISE of 3D BIOLOGY
12–18 YEARS + $1 . 3B = 1 DRUG
90 percent of drug candidates fail during
• Target identification/validation • Assay development • Lead generation DRUG DISCOVERY
5,000 - 10,000
3-5 years
the three phases of clinical trials
Compounds
PRE-CLINICAL
250
1-2 years
• In vitro and in vivo toxicity • ADMET • PK/PD
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.
CLINICAL TRIALS
90% FAIL
6-7 years
10
• Phase I • Phase II • Phase III
REGULATORY APPROVAL
1
1-2 years
1
1 DRUG
Limitations of conventional cell models
CURRENT PARADIGM
NEW PARADIGM
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 e cacy 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 di erently. Animal models are also di cult to humanely and cost-e ectively scale.
higher
iPSCs
3D Models
Immortalized Cell Lines
Small Animal Models
Primary Cells
Large Animal Models
lower
higher
RELATIVE TRANSLATABILITY
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 o er 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 di erentiate 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
BRAIN ORGANOID
LUNG ORGANOID
HEART ORGANOID
PATIENT-DERIVED ORGANOID
INTESTINAL ORGANOID
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.
Physiologically relevant
Disease Modeling
Resemble organ functionality
Multicellular and 3D
Drug Screening
Models major tissue types
Genetically diverse
Precision Medicine
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 o er greater predictability and more
55.30%
biologically-relevant data than 2D cell models, but their wider adoption remains limited. They can be di cult 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
26.10%
“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
25.70%
Cost
24.50%
Access to stable cell lines for growing 3D models
22.20%
Software to track from single cell to 3D organoids and provide deep insights with AI
20.60%
Shorter amount of time to grow 3D models
20.60%
Ability to produce the # of organoids required for screening
19.80%
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
Organoid culture
2D Pre-culture
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.
2
3
4
5
1
Labware hotels
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
Robot arm
Automated centrifuge
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.
Contact Us
Phone: +1.800.635.5577 Web:
www.moleculardevices.com
Email: info@moldev.com Check our website for a current listing of worldwide distributors.
Taiwan/Hong Kong +886.2.2656.7585 Japan +81.3.6362.9109 South Korea +82.2.3471.9531 India +91.73.8661.1198
USA and Canada +1.800.635.5577 United Kingdom +44.118.944.8000 Europe* 00800.665.32860 China +86.4008203586
*Austria, Belgium, Denmark, Finland, France, Germany, Iceland, Ireland, Italy, Luxembourg, Netherlands, Portugal, Spain, Sweden, Switzerland and United Kingdom
©2023 Molecular Devices, LLC
The trademarks used herein are the property of Molecular Devices, LLC or their respective owners. Specifications subject to change without notice. Patents: www.moleculardevices.com/productpatents FOR RESEARCH USE ONLY. NOT FOR USE IN DIAGNOSTIC PROCEDURES.
3/23
Printed in USA
Page 1 Page 2 Page 3 Page 4 Page 5 Page 6 Page 7 Page 8 Page 9 Page 10 Page 11 Page 12 Page 13 Page 14 Page 15Made with FlippingBook. PDF to flipbook with ease