KBP-336

In its quest to stay at the top of the obesity drug market, Eli Lilly is following in Novo Nordisk’s footsteps by pursuing a new class of weight loss drugs. The Indianapolis drug giant said this month it is paying up to $1.4 billion to KeyBioscience to again try to develop dual amylin and calcitonin receptor agonists, or DACRAs, which aim to reduce body weight, control glucose levels and improve insulin action. It’s been seven years in the making. Lilly originally teamed up with the Swiss biotech in 2017 , with plans to develop DACRAs for diabetes and nonalcoholic steatohepatitis. The companies eventually slashed three daily compounds in favor of a once-weekly option, according to Morten Karsdal, CEO of KeyBioscience’s parent company Nordic Bioscience. DACRAs are now shedding its niche status amid the soaring popularity of GLP-1s like Lilly’s weight management drug Zepbound and the hunt for better obesity drugs. Ten years from now, Stifel bankers predict DACRAs, amylin agonists and GIP antagonists could be “good options” for patients who “can’t tolerate GLP-1s.” Novo Nordisk is the furthest along with CagriSema, a combination of its megablockbuster semaglutide — known as Wegovy for weight loss — and an amylin agonist asset known as cagrilintide. It’s expected to have Phase 3 data by the end of the year. Other companies are prepping for the clinic, including Viking Therapeutics and Metsera , which announced a manufacturing deal earlier this month to shore up development capabilities well in advance of commercialization. AstraZeneca , Zealand Pharma and Gubra are also working in the broader amylin class. “As we’re looking for ways to go beyond what a GLP-1 mono-agonist or what a dual-agonist can do in terms of maximum weight loss, adding amylin is probably the next priority in your order of operations for mechanisms you’d want to look at,” Metsera CEO Whit Bernard told Endpoints News . Bernard said Metsera will “soon” enter the clinic with its experimental therapy, a combination of a DACRA, dubbed MET-233, and a GLP-1 injectable, MET-097, which had encouraging early-stage data last month. Executive chair Clive Meanwell previously told Endpoints the combo would be “very competitive” if it induces weight loss of 25% to 30%. Beyond weight loss, Karsdal makes the pitch that DACRAs have additional benefits. “This mode of action should be protecting bone and muscle and other organs,” he said, “so there’s clearly a space for this in the future.” KeyBioscience has been on a winding journey. Its parent company is Danish biomarker and lab services company Nordic Bioscience, which partnered with peptide biotech Unigene Laboratories in 2011 to form a joint venture to create new medicines. Unigene went bankrupt in mid-2013, and Nordic bought out its stake. By 2017, it received $55 million upfront and an undisclosed amount of biobucks as part of a deal with Lilly. But all three assets in that tie-up, including a Phase 2 diabetes drug, wound up on the shelf. Again, KeyBioscience was at a crossroads. “We actually decided with Lilly to terminate those because we wanted to focus on weekly formulations,” Karsdal said, though he declined to detail what led the partners to switch to the once-weekly route after having gone into clinical trials. “I unfortunately cannot comment publicly because the amylin receptor and calcitonin receptor biology is a hot topic for many, and there are some tricks that I cannot disclose,” Karsdal said. KeyBioscience’s once-weekly DACRA known as KBP-336 is now set to enter a global Phase 2 trial investigating the injectable’s ability to reduce weight and tame osteoarthritis pain in people with obesity by the end of the year. KeyBioscience will run the trial, and Lilly has the rights to continue developing it after that, Karsdal said. The trial may include patients who are already on GLP-1s, he said. KBP-336, which is derived from salmon calcitonin , could have broad utility. The calcitonin hormone helps keep bones healthy and can help thwart pain, lending confidence to KeyBioscience’s plans to also test it in osteoarthritis . “We’ve actually been in two Phase 3 studies before with an oral formulation of salmon calcitonin that had an effect on pain in one of the studies, so we’re reasonably convinced that we will get a superior effect on pain,” Karsdal said.