Nordic Bioscience A/S

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.

Eli Lilly is returning to KeyBioscience, a nimble Swiss biotech, seven years after originally linking arms with the startup to work on dual amylin calcitonin receptor agonists for obesity and other conditions. The world’s largest drugmaker by market capitalization will pay up to $1.4 billion to keep working with KeyBioscience on the potential new class of treatments also known as DACRAs. The companies didn’t say how much money was involved in the upfront payment. The tie-up includes an asset that is slated to enter Phase 2 testing by year’s end in people with obesity and osteoarthritis, the companies said Thursday morning. KeyBioscience said it will run the trial, which will include 600 people and look for both body weight reductions and changes in OA pain. Already one of the two GLP-1 leaders in the obesity drug landscape, Lilly continues to place further bets on other mechanisms of action and areas of research. It’s forged obesity pacts applying insights from the “ dark genome ,” the hibernation of the 13-lined squirrel and other areas. Beyond its hallmark tirzepatide franchise, the drugmaker has at least five other experimental medicines in late-stage or Phase 2 testing for obesity. If KeyBioscience follows through with its projected timeline, it could expand Lilly’s obesity pipeline to half a dozen drugs in mid- or late-stage trials by the end of 2024. KeyBioscience’s researchers think the dual agonists can help tamp down on body weight, control glucose levels and improve insulin action. Lilly already has an amylin receptor agonist known as eloralintide in Phase 2 for obesity. The Lugano, Switzerland-based biotech, which is a subsidiary of Danish drug developer Nordic Bioscience, had originally teamed with Lilly in 2017 for $55 million upfront. That pact included DACRAs known as KBP-042, KBP-089 and KBP-056. Lilly removed a Phase 2 of KBP-042/DACRA-042 for type 2 diabetes from its pipeline in the fourth quarter of 2018. Meanwhile, a study of KBP-089 for type 2 diabetes was terminated in 2020. On its website, KeyBioscience says in December 2019 it “reevaluated” its approach, which led to the “abandonment of once-daily injectable DACRAs” and switched to long-acting formulations that could be administered once a week. That pivot led to KBP-336, according to the biotech’s website. The drug entered human studies in the fall of 2021. A Phase 1b was completed in the spring of 2023. It wasn’t immediately clear if KBP-336 is the soon-to-be Phase 2 asset that KeyBioscience highlighted in Thursday’s press release. Editor’s note: This story was updated to include more details on the status of KBP-042 and KBP-089.

Companies to extend collaboration on DACRAs with an additional collaboration molecule and investigation of the DACRA platform within multiple indications LUGANO, Switzerland, Oct. 10, 2024 /PRNewswire/ -- KeyBioscience and Eli Lilly and Company have agreed to extend their collaboration on the development of Dual Amylin Calcitonin Receptor Agonists (DACRA), a new class of potential treatments for obesity and related disorders. This collaboration extends Lilly's rights to KeyBioscience's DACRA platform, including a new molecule that is anticipated to enter a Phase 2 study in people with obesity and osteoarthritis (OA) later this year. KeyBioscience will conduct and complete this study which is planning to enroll 600 people and have dual primary endpoints on body weight and alleviation of OA pain. Under the terms of the extended agreement, Lilly will receive worldwide rights to develop and commercialize DACRA molecules. In exchange for these rights, KeyBioscience will receive an initial payment; downstream consideration totaling up to USD 1.4B, subject to the achievement of certain development, regulatory, and commercialization milestones; and tiered mid-single digits to low double-digits royalties on net sales. " DACRAs have been shown to be potent weight loss agents with potential for additional insulin sensitization. We are extremely excited to move forward with the clinical program, as this class in other Phase 2 trials has shown significant weight loss in people with obesity and clinically meaningful improvement of glycaemic control," said Morten Karsdal, CEO of the parent company of KeyBioscience. " We believe this is a very competitive molecule with very high potency and low immunogenicity risk and look forward to collaborating further with Lilly to advance this important work." Ruth Gimeno, Group Vice President, Diabetes, Obesity & Cardiometabolic Research at Lilly commented; " Dual amylin-calcitonin receptor agonists are an emerging new class of obesity therapies with potential benefits in additional indications. We welcome the expanded collaboration with KeyBioscience and are excited to explore the potential of Key's DACRA molecules in the clinic ." More than a billion people worldwide struggle with obesity, according to the World Health Organization (WHO). While treatment options are evolving, a significant gap remains, particularly in addressing obesity-related complications like OA. OA affects more than 600 million people worldwide, according to WHO, and a considerable proportion of these are with obesity. OA causes debilitating joint pain and limits mobility. Studies confirm that weight loss improves these symptoms. DACRAs, a potential new therapy, may offer a two-pronged approach: promoting weight loss and directly targeting molecular pathways that drive OA progression. About KeyBioscience and Nordic Bioscience KeyBioscience is a fully owned subsidiary of Nordic Bioscience, a Danish Biotech company headquartered in Copenhagen, Denmark. Nordic Bioscience is engaged in clinical research and precision medicine using unique biomarker technologies. Combining experience in preclinical and clinical research enables Nordic Bioscience to help provide faster and smarter detection of signals of the potential clinical viability of drug candidates. For more information about Nordic Bioscience, visit , and for KeyBioscience, visit Refer to: Morten Karsdal; [email protected]; +45 4454 7781 Logo - SOURCE KeyBioscience AG WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED