3D Biology: The paradigm shift in next-gen drug discovery

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.


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 + =

12–18 YEARS

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

3-5 years




1-2 years

• In vitro and in vivo toxicity • ADMET • PK/PD


90% FAIL

6-7 years


• Phase I • Phase II • Phase III



1-2 years



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.



3D Models

Immortalized Cell Lines

Small Animal Models

Primary Cells

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.

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 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

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.






Labware hotels

ImageXpress Confocal high content imaging system

AquaMax microplate washer

SpectraMax microplate readers/ SoftMax Pro Gxp software

ImageXpress Pico automated cell imager


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.

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