GPR3

Novo Nordisk is already an obesity drug heavyweight with its blockbuster seller Wegovy, but its appetite for cardiometabolic drugs continues. The Danish pharmaceutical giant is satisfying that hunger by acquiring a startup with a novel approach to weight loss, marking its second acquisition agreement this month. The latest buyout target is Embark Biotech. According to deal terms announced Wednesday, Novo Nordisk is paying €15 million (about $16.4 million) cash up front. Another €456 million (about $498 million) is tied to milestones. Embark emerged in 2017, spinning out of the University of Copenhagen’s Novo Nordisk Foundation Center for Basic Metabolic Research. The startup was co-founded by Zach Gerhart-Hines, a professor at the university whose research focuses on adipose (fat) tissue biology. Many of the drugs developed for obesity, including Wegovy, suppress appetite. Wegovy is a GLP-1 agonist, mimicking the GLP-1 hormone and prompting the body to produce more of the blood sugar-regulating hormone insulin. While GLP-1 agonists found their first uses as type 2 diabetes treatments, their weight loss effects made them attractive as obesity drugs. Embark had previously said it discovered a novel target that not only suppresses weight loss, but also increases energy expenditure to burn calories. The target is not named in the Novo Nordisk announcement, but Gerhart-Hines’s university lab had made progress researching G protein-coupled receptor 3, or GPR3. This receptor drives thermogenesis, which is another way of saying heat production. In thermogenesis, fat cells take glucose and fatty acids from the blood and burn them as fuel. In mice genetically engineered to overproduce GPR3 in adipose tissue, also called brown fat, the University of Copenhagen scientists found that the test animals were protected from metabolic disease. This protection persisted even as the mice continued to receive a high-calorie diet. The study results were published in 2021 in the journal Cell. The research was funded by the European Research Council, the Independent Research Fund of Denmark, and the Novo Nordisk Foundation. Novo Nordisk says Embark’s development of its target was started under an early collaboration with the pharma giant. The research continued with support from the InnoBooster program at the Innovation Fund Denmark and the BioInnovation Institute. Embark Biotech employees will stay on and work at a newly formed entity called Embark Laboratories, a Danish cardiometabolic disease biotech with a particular focus on therapies emphasizing energy expenditure. Gerhart-Hines is the chief technology officer of Embark Laboratories. Novo Nordisk has the option to acquire from Embark Laboratories selected assets based on Embark Biotech’s discoveries. Those drugs could be further developed in indications such as obesity and type 2 diabetes. “Novo Nordisk has been engaged in obesity research for 25 years, and we continuously search for new ways to address this serious chronic disease,” Brian Finan, vice president of obesity research at Novo Nordisk, said in a prepared statement. “We are excited about the opportunity to advance Embark Biotech’s lead program and look forward to co-creating novel treatments for cardiometabolic diseases with Embark Laboratories to complement our in-house R&D.” The Embark acquisition gives Novo Nordisk a different approach to metabolic disorders than the one taken by Inversago, a startup whose acquisition agreement was announced three weeks ago. Clinical-stage Inversago is developing small molecules that block cannabinoid receptor type 1, or CB1, a receptor found in the central nervous system and the gastrointestinal system. Blocking this receptor can suppress appetite. If Inversago’s drug candidates achieve milestones, Novo Nordisk could end up paying its shareholders more than $1 billion. Embark is not the only startup aiming to boost cellular energy expenditure as a way to lose weight. Nearly a year ago, Rivus Pharmaceuticals unveiled a $132 million Series B round of financing to support mid-stage clinical development of drugs it calls controlled metabolic accelerators. These small molecules target energy-producing components of cells called mitochondria, boosting their energy expenditure. The science of Charlottesville, Virginia-based Rivus comes from Gencia, a biotech focused on mitochondria-targeting drugs.

Embark Biotech has been on Novo Nordisk’s radar for years. Novo Nordisk is continuing to seek out obesity assets, paying 15 million euros ($16 million) to snap up Embark Biotech in its second weight loss takeover in quick succession.  The clinical and emerging commercial success of GLP-1 drugs developed by Novo Nordisk and Eli Lilly in diabetes and obesity has turned weight loss into one of the hottest categories in pharma—and sparked a scramble to snap up next-generation candidates. Lilly inked a deal worth $1.9 billion to buy Versanis Bio last month, and Novo Nordisk struck back in August with the buyouts of Inversago Pharma and Embark. Copenhagen-based Embark has been on Novo Nordisk’s radar for years. The biotech spun out of the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen in 2017, was incubated at Novo Seeds and began collaborating with Novo Nordisk in 2018. Embark is built on research carried out at the lab of Zachary Gerhart-Hines, Ph.D. The lab studied a signaling axis between the adipose tissue, gut and central nervous system, leading to the identification of targets that are involved in fat energy expenditure.   Novo Nordisk’s statement about the takeover lacks details of the targets, and Embark’s website has been replaced by a link to the press release about the acquisition. But an archived version of the biotech’s website shows the company was developing agonists of EMB1, a previously undescribed adipocyte G-protein coupled receptor, in the belief they drive weight loss by raising glucose uptake and energy expenditure. In February, Embark’s site listed its long-lived EMB1 peptide program as being in preclinical development in preparation for first-in-human trials. The biotech received grant money to support preclinical safety tests late last year. Embark’s website also discussed GPR3, a constitutively active G-protein coupled receptor that it called an “important regulator of thermogenic adipose activity.” Researchers at Embark and its partners published a paper on GPR3 in 2021, in which they described how “mice were completely protected from developing diet-induced obesity despite maintaining comparable levels of food intake.” As well as the 15 million euro upfront payment, Novo Nordisk is committing up to 456 million euros ($496 million) in commercial milestones to acquire Embark’s science. All the biotech’s employees will transfer to a new group, Embark Laboratories, to “continue their work and scientific journey.” The new company is focused on cardiometabolic disease and has formed a three-year obesity R&D collaboration with Novo Nordisk.

Dive Brief:Novo Nordisk is adding to its recent string of obesity-related dealmaking, announcing Wednesday it has agreed to pay 15 million euros, or about $16 million, to buy Embark Biotech, a startup it helped found from a research center at the University of Copenhagen.Per deal terms, Embark shareholders could receive up to 456 million euros in additional payments based on achievement of certain development, regulatory and commercial goals. The startups staff will continue their research under a new company called Embark Laboratories.Fueled by quickly growing sales of its weight-loss drug Wegovy and diabetes therapy Ozempic, Novo has secured a leading position in obesity treatment, which could be worth tens of billions of dollars in annual sales. The Danish firm is looking to strengthen its hold through dealmaking, with the latest acquisition coming three weeks after the announced buyout of Canadian biotechnology company Inversago Pharma.Dive Insight:Embark got its start at the Novo Nordisk Foundation Center for Basic Metabolic Research, where research conducted by Zach Gerhart-Hines, Jakob Bondo Hansen and Thue Schwartz gained seed backing from Novo Holdings and a collaboration with Novo Nordisk itself.Gerhart-Hines and Schwartz have published research on two proteins, FFAR4 and GPR3, that regulate energy expenditure and the breakdown of fatty tissue. In announcing the deal, Embark cited a novel target that suppresses appetite, increases energy expenditure and enhances insulin sensitivity.In previous disclosures, Embark said it had identified a peptide drug for cardiovascular and metabolic disease and a small molecule energy expenditure activator that it was investigating for obesity.Novo set a new standard in obesity treatment when it repurposed its daily blood-sugar-lowering injection Victoza into a weight-loss drug called Saxenda. A weekly diabetes treatment Ozempic followed, which it sells in weight-loss as Wegovy, although Ozempic is widely used off-label to treat overweight people.These drugs regulate blood sugar by activating a hormone called GLP-1. Eli Lilly is looking to dethrone Novo with Mounjaro, a dual-acting injection that activates GLP-1 and another target called GIP. Mounjaro has been approved in diabetes and could be launched soon for weight loss.In response, Novo is beefing up its diabetes and weight-loss pipeline, where it has around nine novel projects in clinical trials.With the Inversago and Embark deals, Novo will add up to five experimental drugs in diabetes, obesity and metabolic diseases. '