amylin

COPENHAGEN, Denmark I April 24, 2025 I Zealand Pharma A/S (Nasdaq: ZEAL) (CVR-no. 20045078), a biotechnology company focused on the discovery and development of innovative peptide-based medicines, today announced that the first participant has been enrolled in ZUPREME-2, a Phase 2b trial in people with overweight or obesity and type 2 diabetes comparing once-weekly subcutaneously administered petrelintide, a long-acting amylin analog, versus placebo with regards to efficacy and safety 1 . “We are excited to announce the initiation of ZUPREME-2, the second Phase 2 trial initiated with petrelintide and an important part of our clinical development plan for establishing petrelintide as a best-in-class alternative to incretin-based therapies and a future foundational therapy for weight management”, said David Kendall, MD, Chief Medical Officer at Zealand Pharma. “ Amylin agonism has shown great potential to provide clinically meaningful weight loss and may also provide additional improvements in glycemic control in people with overweight or obesity and type 2 diabetes, and we look forward to evaluating the efficacy and safety of petrelintide as a weight loss therapy in this population.” About ZUPREME-2 ZUPREME-2 is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, Phase 2b clinical trial (NCT06926842). The trial will compare three doses of once-weekly petrelintide with placebo, when added to a reduced-calorie diet and increased physical activity in participants with overweight or obesity and type 2 diabetes. The trial includes a screening period, a dose escalation treatment period up to 16 weeks with dose escalation every fourth week followed by a maintenance treatment period until week 28, and a follow-up period after treatment is completed until week 38. ZUPREME-2 is expected to enroll a total of approximately 200 participants. The primary endpoint in the trial is the percentage change in body weight from baseline to week 28. Secondary endpoints include, but are not limited to, body weight loss of ≥5% and ≥10%, absolute change in body weight, change in waist circumference, change in hemoglobin A1c (HbA1c), change in high-sensitivity C-reactive protein (hsCRP), change in fasting glucose, and change in fasting lipids. For more information about the ZUPREME-2 clinical trial of petrelintide, please visit https://clinicaltrials.gov/study/NCT06926842 . About petrelintide Petrelintide is a long-acting amylin analog suitable for once-weekly subcutaneous administration that has been designed with chemical and physical stability with no fibrillation around neutral pH, allowing for co-formulation and co-administration with other peptides 2 . Amylin is produced in the pancreatic beta cells and co-secreted with insulin in response to ingested nutrients. Amylin receptor activation has been shown to reduce body weight by restoring sensitivity to the satiety hormone leptin 3,4 , inducing a sense of feeling full faster. Current clinical data or pre-clinical data suggest a potential of petrelintide to deliver weight loss comparable to GLP-1 receptor agonists but with improved tolerability for a better patient experience and high-quality weight loss. In November 2024, Zealand Pharma presented detailed results from the Phase 1b 16-week multiple ascending dose (MAD) trial at the Obesity Society Annual Meeting (ObesityWeek) 2024. For the presentation, please visit Scientific publications – Pipeline – Zealand Pharma . Petrelintide is also being evaluated in ZUPREME-1, a Phase 2 trial in participants with overweight or obesity (NCT06662539), evaluating five target doses of petrelintide up to 9 mg over 42 weeks of treatment. Enrollment and randomization in ZUPREME-1 was completed in three months. In March 2025, Zealand Pharma and Roche entered a collaboration and license agreement to co-develop and co-commercialize petrelintide as a future foundational therapy for people with overweight and obesity. The closing of the transaction is subject to regulatory approvals and other customary closing conditions. The parties expect that the agreement will close in the second quarter of 2025. About Zealand Pharma Zealand Pharma A/S (Nasdaq: ZEAL) is a biotechnology company focused on the discovery and development of peptide-based medicines. More than 10 drug candidates invented by Zealand Pharma have advanced into clinical development, of which two have reached the market and three candidates are in late-stage development. The company has development partnerships with a number of pharma companies as well as commercial partnerships for its marketed products. Zealand Pharma was founded in 1998 and is headquartered in Copenhagen, Denmark, with a presence in the U.S. For more information about Zealand Pharma’s business and activities, please visit www.zealandpharma.com . Sources 1. ClinicalTrials.gov. Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity and Type 2 Diabetes (ZUPREME 2). Available at https://clinicaltrials.gov/study/NCT06926842 . Last accessed April 2025. 2. Eriksson et al. Presentation at ObesityWeek, November 1–4, 2022, San Diego, CA. Link: https://www.zealandpharma.com/media/0gnfxg4b/zp8396-sema-coformulation-obesityweek-2022.pdf . 3. Mathiesen et al. Eur J Endocrinol 2022;186(6):R93–R111. 4. Roth et al. Proc Natl Acad Sci U S A 2008;105(20):7257–7262. SOURCE: Zealand Pharma

Dive Brief:Novo Nordisk is expanding its pipeline of obesity medicines, announcing Monday it will pay China-based United Laboratories International Holdings $200 million upfront to license an experimental triple agonist weight loss shot that could take on Eli Lillys retatrutide.Per deal terms, Novo will have commercialization rights to the drug outside of China and nearby marketing territories, and could owe up to an additional $1.8 billion based on achievement of certain milestones by the drug, called UBT251. Novo would also pay royalties on sales in its marketing territories.Novo had a big head start in obesity, getting the GLP-1 drug Wegovy to people with obesity five years ahead of Eli Lilly and its medicine Zepbound. But Lilly is catching up quickly, showing in testing that Zepbound helps people lose more weight than Wegovy and closing the sales gap, which stands at $4.9 billion in 2024 to Wegovys $8.4 billion.Dive Insight:Both Novo and Lilly struggled to meet demand for their obesity drugs, forcing them to spend billions of dollars to boost their manufacturing capacity. With that issue now largely resolved, Novo is turning its attention to the competitive landscape, where it is facing a stiff challenge from Lilly and other potential rivals like Amgen, Pfizer, Zealand and Viking Therapeutics.Novo pioneered the use of drugs stimulating a gut hormone called GLP-1 to help people with obesity lose weight. Lilly showed that, by acting on a second one called GIP, Zepbound could improve GLP-1s efficacy. Now drugmakers are experimenting with the use of other related pathways called glucagon and amylin although Novos initial effort in that area, combining GLP-1 and amylin, has underperformed expectations.Lilly is leading in triple-acting drugs, too, with an experimental shot it calls retatrutide that could have Phase 3 results next year. Novo advanced a tri-agonist into Phase 1 trials last year, but with the deal announced today it would have a drug that has already completed a Phase 1 dosing trialThe addition of a candidate targeting glucagon, as well as GLP-1 and GIP, will add important optionality to our clinical pipeline, as we look to develop a broad portfolio of differentiated treatment options that cater to the diverse needs of people living with these highly prevalent diseases, said Martin Holst Lange, Novos executive vice president for development, in a statement.Novo said Uniteds medicine had a similar side effect profile as Wegovy, Zepbound and drugs in the class, and helped people who completed the trial lose 15.1% of their body weight over 12 weeks, compared with a 1.5% increase for people who got placebo.The new tri-agonist will join an already beefy pipeline, which includes the GLP-1/amylin drug CagriSema, for which Novo still has high hopes, a version of its GLP-1 diabetes pill Rybelsus in obesity and various combinations of GLP-1, GIP and amylin. '

Zealand first announced that it was seeking a development partner in August 2024. Credit: Liudmila Chernetska via Getty Images. Zealand Pharma has named Roche as a development and commercialisation partner for its lead obesity candidate petrelintide, after a seven-month search. Under the deal, Zealand will receive an upfront payment of $1.65bn, with the potential for milestone payments bringing the total deal value to $5.3bn, depending on Phase III trials and commercial performance. Zealand and Roche will co-develop and co-commercialise Zealand’s amylin analogue petrelintide as a monotherapy, and in combination therapies. The first planned combination will pair petrelintide with Roche’s glucagon-like peptide 1/gastric inhibitory polypeptide (GLP-1/GIP) agonist candidate CT-388. Inherited by Roche through its $2.7bn acquisition of Carmot Therapeutics, CT-388 has demonstrated efficacy in early trials . In a Phase Ib trial (NCT04838405), participants taking the therapy achieved a mean placebo-adjusted weight loss of 18.8% at 24 weeks. CT-388 is currently being studied in two Phase IIb clinical trials in people with overweight/obesity with (NCT06628362) and without type 2 diabetes (NCT06525935). As part of the collaboration, Zealand will contribute $350m to support the study of the CT-388/petrelintide combo. The companies will share profits and losses on a 50/50 basis in the US and Europe while Zealand will receive tiered royalties on net sales in other global markets. Zealand first shared that it was eyeing up a partner to study and commercialise its lead weight loss candidate back in August 2024. However, its failure to announce a deal in its February earnings report last month disappointed investors . At the time, CEO Adam Steensberg reassured stakeholders that the company was “exactly where it wants to be in the process”. Zealand has delivered this promise with the Roche partnership now secured. The collaboration marks Zealand’s progression into the obesity space, which is dominated by GLP-1 receptor agonists (GLP-1RAs) such as Novo Nordisk’s semaglutide (branded as Wegovy and Ozempic), and Eli Lilly’s tirzepatide (branded as Mounjaro and Zepbound). Petrelintide is currently being investigated in the Phase II ZUPREME clinical trial (NCT06662539). While GLP-1RAs such as semaglutide work by stimulating insulin secretion, reducing glucagon levels, and slowing gastric emptying, amylin analogues such as petrelintide act through a different mechanism. By mimicking the hormone amylin, they suppress glucagon secretion, slow gastric emptying, and restore sensitivity to the satiety hormone leptin. Zealand believes this distinct mode of action could position petrelintide as a best-in-class therapy in obesity and diabetes. “We strongly believe that petrelintide holds potential as a foundational therapy for weight management,” said Steensberg in the 12 March announcement accompanying the deal. Investor confidence in Zealand’s obesity pipeline has remained high. In June 2024, the company raised $1bn through a share offering, surpassing its original target of $900m. In January 2024, Zealand secured an additional DKr1.45bn ($204m) in funding for its obesity pipeline through a private placement and directed share issue to US investment firms. Zealand’s other major obesity candidate , survodutide, a glucagon/GLP-1 receptor dual agonist developed with Boehringer Ingelheim, is already in Phase III trials for obesity and metabolic dysfunction-associated steatohepatitis (MASH). Rates of obesity across populations are increasing, and the market for obesity drugs is set to reach $37.1bn across the seven major markets (US, UK, Germany, France, Italy, Spain, and Japan), by 2031, according to a GlobalData report. GlobalData is the parent company of Pharmaceutical Technology.