CN Bio is a cell culture company whose mission is to transform the way human-relevant pre-clinical data is generated by developing the most complete model of the human ‘body-on-a-chip’ in the laboratory. Achieving this is what drives the company’s future initiatives, CEO Dr David Hughes told Lu Rahman.
CN Bio hit its first major milestone in 2018 when its Microphysiological System (MPS), the PhysioMimix OOC, was launched. Designed to bridge the gap between preclinical in vitro testing and human clinical trials, it incorporates technology licensed from collaborators at Massachusetts Institute of Technology (MIT) and allows researchers to recreate healthy and diseased human biology in the lab by culturing predictive 3D tissue-based models (otherwise known as organ-on-a-chip (OOC)).
“These advanced in vitro models typically comprise human cells and tissues whose phenotypes and functions mimic those in vivo. When drugs are added to these models, they generate translationally relevant pre-clinical data. Recently we achieved the second milestone in our body-on-a-chip journey, linking multiple organ models together via microfluidics that mimic inter-organ blood flow,” says Hughes.
These powerful humanised solutions have the potential to become standard tools in the drug discovery workflow and facilitating this is key to the company’s future growth. “Our current initiatives at CN Bio are focussed on making MPS as accessible as possible by expanding our portfolio of applications via new assays, novel product development, and by offering access through Fee-For-Service,” he adds.
As well as being CEO, Hughes leads the development of CN Bio’s products and science as Chief Technical Officer. “Being close to the science is important, as it helps me understand the applications our customers really need, and consequently the business strategy we should follow,” he reveals.
The business boasts success working with key global pharmaceutical and biotech companies. Hughes is clear on why this is: “Ultimately, drug discovery efforts fail when traditional pre-clinical approaches, such as 2D cell culture or animal models, neglect to predict human responses. With around nine out of every ten drug candidates failing to win approval in clinical trials, this has huge implications for the overall speed and cost of drug development. Companies are receptive to ways to develop safe and efficacious therapeutics, faster and more cost effectively. What we have to offer fits this remit.
“Right at the beginning of drug discovery, our human-relevant models can help to identify and validate drug targets to prevent an irrelevant-in, irrelevant-out cascade through the whole process. With safety and efficacy concerns being the principal causes for failure in Phase I and II clinical trials, predictive models like OOC can be used to validate lead or candidate efficacy and investigate toxicity further upstream. Essentially, if we can help pharma more accurately identify promising candidates and fail those lacking efficacy or showing toxicity earlier in their process, that’s beneficial..”
Collaboration is important to the business and CN Bio boasts some exciting examples in this respect. “We understand our solutions are new and disruptive, so we pride ourselves on being collaborative and supporting pharma/biotech to demonstrate value and optimise the fit of our systems in their workflows. Collaboration is key to keeping our products where they need to be – at the cutting edge. We collaborate closely with, and license technology, from leading academic bio-engineering groups including MIT and Vanderbilt University. With MIT, we demonstrated the concept of human-body-on-chip through a DARPA funded initiative where 10 different organs were cultured together in the lab for a month. A recent collaboration with the University of Cambridge saw our in-vitro NASH (Non-alcoholic steatohepatitis) model uncover a novel, and potentially druggable, target in this important disease,” Hughes says.
By collaborating directly with the FDA (US Food and Drug Administration), Hughes reveals they are learning together with the regulator how MPS can impact regulatory science, with an eye on potential use in IND submissions.
“We believe this collaboration is pivotal and will accelerate the pace of MPS adoption within drug discovery,” he adds. “We have found drug discovery companies are more than willing to collaborate over new developments, which is a win-win. Their input accelerates the pace of our journey towards new applications, while early access to novel technologies offers them the chance of a head start versus their competitors, a solution matched to their needs.”
Achievements, of course, don’t come without expertise. Dr Hughes acknowledges that CN Bio’s achievements are driven by its people, “whose unique expertise and experience in this emerging field ensure we develop the right products and applications to enable success for our customers.”
He believes the company has two key differentiators versus its competitors. One of these is the ease of use of its systems. “We enable incredible biology but take away the fiddliness and complexity often associated with OOC technologies,” he states.
The other is that as the company’s microfluidics solutions enable the linking of multiple organs models together , scientists now have the potential to rapidly to develop insights that only the interconnection of organs and tissues can bring.
“By combining people and technology, our service business enables us to respond to customers needing to act quickly, or who wish to access our proprietary NASH model. In just weeks, we are able to provide answers to complex biological questions or produce efficacy and toxicity data from human relevant models,” says Hughes.
CN-Bio helps pharma and biotech companies improve the effectiveness and efficiency of pre-clinical drug testing. “We want to provide researchers with the tools to do the very best science possible, which means delivering data that is in vivo representative,” says Hughes. “The combination of 3D cell culture and microfluidics in our products enables pharma scientists to produce unique disease models and conduct experiments which would previously have required animals, been impractical or even impossible. Specific examples include the use of gene editing/silencing reagents to knock down targets and study the effect on a disease model over many weeks, opening up the ability to validate a target hypothesis, and the testing the safety and efficacy of new human specific modalities, for which animal models are unsuitable or unavailable.”
The company’s customers work in a range of areas – metabolic diseases, oncology, infectious diseases. Hughes is clear on the impact CN Bio’s technology can offer the drug discovery sector: “The potential for our technology is far reaching, but toxicity testing represents an early area where CN Bio can offer very clear benefits to customer workflows. Single- and multi-organ MPS technologies are designed to achieve phenotypes matching human organs or tissues and to allow crosstalk, making them well-suited to the evaluation of safety. By connecting a liver tissue with another organ, our MPS offer the opportunity to study reactive metabolite driven toxicity or simultaneously evaluate drug absorption and metabolism. Turning to disease models, we have already demonstrated the ability to model complex metabolic (NASH) and infectious (HBV) diseases, with programs on COVID not far behind. The big opportunity here is to incorporate more of the human immune system into these models, making it possible to model new diseases and therapies (eg. checkpoint inhibitors). We have already demonstrated that CN Bio’s MPS system can support circulating immune cells.”
Of course, this year has been all about COVID-19, nowhere more so than in the drug discovery space. Its impact on businesses has been evident, including CN Bio. Hughes sums it up: “Most obviously, many companies have initiated vaccine and therapy programs targeting the SARS-CoV-2 virus, increasing the need for discovery and pre-clinical tools for the study of virology and immunology. The lockdowns and general uncertainty created by the pandemic across the world have limited access to pharmaceutical and contract research laboratories, slowing progress on discovery projects and experimental studies. Customers are looking towards service providers like CN Bio who have in-house capacity and are able to respond rapidly. Many are actively considering options such as replacing in vivo studies with in vitro experiments which offer shorter study time and faster data, making them less vulnerable to the unpredictable nature of the pandemic.”
Volume 22, Issue 1 – Winter 2020/21
Dr Hughes was appointed CEO of CN Bio in 2018, having previously served the company as CTO. He oversees corporate strategy, bringing deep technical knowledge and strong understanding of the OOC market to this role. He led the company’s participation in a key five-year $26M DARPA contract alongside the Massachusetts Institute of Technology to build a human body-on-a-chip. He holds a Masters in Engineering Science and a Doctorate in Chemical Engineering from the University of Oxford.