Molecular Devices, a life science tools company, has long been associated with its plate reader, imaging technology and software. Now, the company is making significant investments in organoid technologies, which it views as the future of drug discovery and development. These investments include the acquisition of organoid provider Cellesce, a developer and manufacturer of patient-derived organoids (PDOs). The acquisition complements Molecular Devices’ current activity in the field. As Susan Murphy, President of Molecular Devices, put it, “What Molecular Devices does is help customers develop and grow organoids.”
Currently, drug discovery and development are primarily done using 2D human models and animal testing, which are regarded as not being fully representative of the complexity of human cell morphology and behavior. 3D organoids present an alternative, providing an environment closer to in vivo conditions. As Vicky Marsh-Durban, PhD, CEO of Cellesce, explained, “Organoids are really about recapitulating human tissues in a dish. They are really unique in terms of the fact that they are grown from adult stem cells or from other stem cells, including iPSCs, and they’re grown in three dimensions and they will spontaneously organize to form features that recapitulate those seen in the primary patient tissue.” She added, “Obviously, [they are] completely different from two-dimensional cells in a dish in terms of the fact that they have this 3D morphology and 3D structure which recapitulates the tissue of origin. The tissue of origin can be normal tissue or diseased tissue.”
But one of the drawbacks to widespread use of organoids for drug discovery and development has been time, labor requirements and low-throughput workflows. Cellesce’s PDOs address these and other issues. As Ms. Murphy told IBO, “It’s extremely hard to grow organoids, and no one has the ability to grow reproducible, scalable, reliable organoids to be able to screen. You want to be able to have that pool of similar organoids to start your screen to go through the drug discovery process.” Cellesce’s large-scale manufacturing employs proprietary bioreactor and bioprocess technology, allowing large-volume, quality-controlled production of PDOs.
“Being able to have and provide our customers with either off-the-shelf or customized or manufactured organoids at scale with our workflow and solutions really brings us a complete turnkey solution.”
Molecular Devices’ expertise and customer base can help promote adoption, Ms. Murphy. “Being able to have and provide our customers with either off-the-shelf or customized or manufactured organoids at scale with our workflow and solutions really brings us a complete turnkey solution.” She emphasized that Molecular Devices is well-positioned to do this. “We have the hardware and the software to not only acquire the images but then also do the analysis. We have the high-content imaging that is able to image in 3D as well as [process] all that data.” In addition, Molecular Devices’ established presence in the laboratory tools sector and resources can also assist in wider use of Cellesce offerings. “We can really utilize that engine to educate and make people aware of this process that people are trying to solve that don’t know and don’t have a way to do so.”
We’re hoping to open that up with primary screening, because it’s not happening today in primary screening. Immediately, we’re saying we can offer up to 100,000 compounds screens utilizing Cellesce organoids and molecular devices, hardware and software.”
One area where the use of organoids has been particularly problematic is large-scale screening in early drug discovery, one of many steps in the drug development and discovery process, Cellesce’s technology provides a solution throughout the process, including screening, according to Ms. Murphy. “There’s primary screening, secondary screening [and] toxicology—organoids can be used through that entire drug discovery journey…It’s not just the ADME/Tox phase. It’s really across the entire portfolio of how drugs get to patients that you can utilize organoids [for]. To be able to have the reproducibility of those organoids over that process is what customers don’t have a way to do today.” Regarding Molecular Devices’ offerings, she highlighted, “We’re hoping to open that up with primary screening, because it’s not happening today in primary screening. Immediately, we’re saying we can offer up to 100,000 compounds screens utilizing Cellesce organoids and molecular devices, hardware and software.”
Besides expanding screening applications, Cellesce’s PDOs can also enable new research approaches. “In general, there are a lot of disease models that aren’t even explored today because there aren’t models available,” said Ms. Murphy. “By being able to have organoids, we’re going to be actually opening up additional types of drug therapies and research that don’t even exist today.” Cellesce currently offers colorectal cancer organoids, breast cancer organoids and “healthy” intestinal PDOs, but is developing additional offering to address pancreatic and lung cancer.
There are challenges for organoids’ wider adoption. “I think because it’s an evolving space and people have been doing 2D screening for so long, anytime you change an experiment it takes a little bit of time,” observed Ms. Murphy. “People want to know ‘well, what’s the first drug that’s going to go through [clinic]?’ but it takes a while to get to clinic.” Dr. Marsh-Durban further noted, “I think what [Cellesce] found really is that there are definitely challenges around educating customers, what they can and can’t do with the technology, what the models can and can’t tell you, and then how you would utilize them in their assays.” Here, Molecular Devices can provide resources. “I think this is really where the union of Cellesce and Molecular Devices really comes into its own because, obviously, [we’re] looking then at more imaging-based screening,” explained Dr. Marsh-Durban. This enhances customers’ current options. “We’ve had a lot of customers that want to put organoids into very simple readouts that really don’t give you the richness of the biology that you get within organoid models.”
Another opportunity for Cellesce technology is its use to directly screen patient samples for assistance in patient treatment. This is already being done at Molecular Devices’ Organoid Innovation Center. “In the Organoid Innovation Center, we basically have a workflow where you can develop organoids and be testing organoids for screening, and we have customers that we’ve helped set up these types of facilities where they are taking customer sample and testing and going back and working on those recommendations of what would work,” said Ms. Murphy. She cited Cincinnati Children’s Hospital Medical Center as one such customer.
By joining Molecular Devices, Cellesce will be able to further the commercialization and development of its technology. Molecular Devices gains organoid expertise, additions to its organoid workflows and new technology that could be the future of drug discovery.