The Swiss startup Nagi Bioscience aims to speed up drug and chemical safety testing by automating research on a worm called Caenorhabditis elegans.
For companies developing a drug or chemical product, there are many ways to predict the safety of their compound in humans. They can test the drugs in cell cultures, which are cheap but not a great model of a living organism. Or they can use lab animals like mice, which are a better living model, but can be expensive and ethically problematic.
C. elegans: bridging the preclinical gap
The worm C. elegans is an emerging animal model that could bridge the gap between cell cultures and vertebrate animal models. After more than 60 years of research, the worm’s genetics, physiology and behavior have been well characterized. The tiny animal is also widely considered as a cheaper and more ethical alternative to mice.
“C. elegans is one of the most established models in biology,” said Matteo Cornaglia, CEO and founder of the Swiss company Nagi Bioscience. “It doesn’t apply to all possible fields of research in human health, but there are plenty of validated routes of research where the translation is very good.”
The need for automation
One main sticking point for using C. elegans in routine drug discovery and toxicology has been the need for trained researchers. Tasks like picking up, monitoring and moving these animals takes a lot of manual labor.
To solve the problem, Nagi Bioscience is developing a robotic, worm-on-a-chip system to culture and screen C. elegans. The worms themselves are grown in disposable microfluidic cartridges, which are plugged into an automated device to pump in nutrients, apply drugs of interest and snap pictures of the worms in their culture. Up to four cartridges, and more than 1,000 worms, can be screened at a time.
“This is super standardized because no human touches anything,” said Cornaglia. “We can control temperature, food — everything about the culture. We can treat them with the compounds of interest and see the impact on the worms.”
From academia to founding Nagi Bioscience
Cornaglia and his colleagues spun the firm out of École Polytechnique Fédérale de Lausanne in 2019. This came after years of research into their worm-on-a-chip technology, including Cornaglia’s PhD project.
“It was a very exciting learning experience,” recalled Cornaglia. “It’s also very motivating to have a purpose beyond your research.”
Nagi has spent the early years of its life selling drug and chemical screening services to pharma, cosmetics and agrochemical clients. By early 2023, the company plans to launch a range of worm-on-a-chip devices that can be used in customers’ labs. To fund this trajectory, Nagi raised €1.6 million ($1.8 million) in a seed financing round in 2019, and plans to raise more cash in a Series A round.
Aging research with C. elegans
For biopharma clients, testing their compounds in a whole animal model has multiple advantages. As the procedure is cheaper and more scalable than mouse experiments, drug developers can test the drug in a whole organism earlier on in development than they normally would be able to. According to Cornaglia, this can derisk the project earlier on with whole-animal data.
In particular, Nagi’s technology has a lot of potential to appeal to companies treating age-related diseases, which often use C. elegans as a model of lifespan.
“Because of our technology, [clients] can keep [C. elegans] and track them for the whole duration of their lifespan, which is about two weeks on average,” remarked Cornaglia. “You can see a whole organism aging and dying naturally in less than a month.”
Making drug discovery efficient
There have been several initiatives in academic circles to smooth the process of screening C. elegans, with names ranging from WormMotel to the Lifespan Machine to WormBot. In the U.K., a firm called Magnitude Biosciences spun out of the University of Durham in 2018 to offer contract research organization (CRO) services based on C. elegans. However, Cornaglia explained that Nagi stands out in the race to bring full automation to the field.
Running a hybrid business model has been a challenge for the Nagi team. And then there are other obstacles in the use of C. elegans in aging studies. For example, a microfluidic setup doesn’t always resemble the worm’s natural soil habitat and can cause stress to the animal. And some researchers have found it tough to assess the precise time of death for the worms without an expert manually scrutinizing the footage.
Nonetheless, C. elegans remains a promising way to merge the high-throughput nature of in vitro biology with whole-organism screens. There are many other types of technology in development to accelerate preclinical drug development, including organoids, organs-on-chips and tissue bioprinting. All together, this could steadily reduce the amount of work required in mice and other vertebrates, cutting costs while improving the translation of preclinical work to humans.