The Swiss startup EraCal Therapeutics has signed a research partnership with the Danish pharmaceutical giant Novo Nordisk to search for treatments controlling food intake and other factors contributing to obesity.
Under the joint project, EraCal and Novo Nordisk will research targets for obesity treatments by identifying molecules that can control appetite and improve metabolic health. The drugs will be screened in an emerging drug discovery model: zebrafish larvae. The CEO of EraCal, Josua Jordi, declined to specify the financial terms of the deal.
Zebrafish have been a hot topic for the drug discovery pipeline since the early 2000s, but it’s only been in the last few years that their utility has matured. As of 2020, there were eight molecules in clinical trials that had been developed in zebrafish.
Preclinical drug development typically involves screening candidate drugs in cultured cells in bulk before testing them in animals, often mice. Zebrafish larvae can be grown in large volumes that are reminiscent of in vitro techniques, while still being similar enough to humans to predict the effects of a drug on the nervous system.
According to Jordi, EraCal is capable of screening mass quantities of zebrafish, which have a blood-brain barrier and biology similar to humans. “You cannot look at 1,000 mice and measure their food intake in a non-brute-force approach,” said Jordi. “EraCal looks at multiple behaviors including food intake in 1,000 fish a day in a fully quantitative manner.”
EraCal is a spinoff from the University of Zurich, where Jordi was a graduate student, and Harvard University, where he was a postdoctoral researcher working on neurophysiological drivers of feeding behavior in zebrafish. EraCal is a portmanteau of ‘erase calories.’
“EraCal can screen thousands of interventions for their impact on food intake in vivo,” said Jordi. The startup’s platform screens potential obesity treatments for bioavailability, toxicity, and behavioral side effects in zebrafish. “How do you know if a treatment that reduces food intake in an animal is not doing so by inducing sleep or nausea or interfering with other key brain functions? One way is to measure the brain output, ie. behavior, in a variety of different complex tasks and look for selectivity of your appetite suppressors in vivo,” said Jordi.
Weight loss pharmaceuticals have been studied for almost a century. One example is 2,4-dinitrophenol (DNP), which was developed in the 1930s. DNP disrupts the process of storing energy in the cells, making the body release that energy as heat instead. Unfortunately, DNP can also cause life-threatening increases in body temperature and has never been approved in the modern day. Several drugs were approved and then pulled in the 1990s, after reports of heart valve damage, heart attacks, risks of cancer, and suicidal thoughts.
There was some progress in the obesity treatment field last year. Novo Nordisk’s diabetes drug semaglutide targets areas of the brain that regulate appetite. In June 2021, the drug was approved by the FDA to assist weight management in overweight patients. Demand for the drug has remained high since, even weathering a rash of manufacturing issues.
Outside of the Novo Nordisk partnership, EraCal is developing its own candidate drug, which reduced the bodyweight of mice by 14% in two weeks in one study. Additionally, the experimental obesity treatment showed no signs of common side effects of conventional weight loss drugs such as cognitive impairment and nausea. If development proceeds smoothly, the company expects to reach the market in 2028.
Cover image via Elena Resko