Company announcement – No. 27 / 2024

Zealand Pharma announces topline results from the mechanistic investigator-led DREAM trial with low doses of GLP-1/GLP-2 receptor dual agonist dapiglutide

• Mean weight loss of up to 4.3% after 12 weeks with low doses of dapiglutide treatment
• Dapiglutide was assessed to be well-tolerated
• Tolerability profile observed suggests doses investigated were at the lower end of the therapeutic range
• Much higher doses of dapiglutide are being investigated in the ongoing 13-week Phase 1b trial, with topline results expected in the second half 2024

Copenhagen, Denmark, 23 May 2024 – Zealand Pharma A/S ("Zealand") (Nasdaq: ZEAL), (CVR-no. 20 04 50 78), a biotechnology company focused on the discovery and development of innovative peptide-based medicines, today announced topline results from the DREAM trial (Dapiglutide for the Treatment of Obesity), the investigator-led clinical trial designed to evaluate the potential for weight loss and to gain key mechanistic insights into the effects of low doses of GLP-1/GLP-2 receptor dual agonist dapiglutide following a 12-week treatment period. No lifestyle interventions, such as diet or exercise, were part of the trial.

Treatment with dapiglutide at doses of 4 and 6 mg resulted in an observed numerical mean weight loss change from baseline of 2.9% (p=0.483) and 4.3% (p=0.077) after 12 weeks, respectively, compared to 2.2% with placebo (primary endpoint).¹

“We are encouraged by the reductions in body weight observed in this investigator-led mechanistic trial using low doses of dapiglutide. These results are in line with the outcomes observed with shorter term treatment using lower doses of other incretin-based therapies,” said David Kendall, MD, Chief Medical Officer of Zealand Pharma. “Our ongoing 13-week Phase 1b dose-titration trial is currently evaluating higher doses of dapiglutide up to 13 mg, and based on the tolerability profile observed to date, we will seek to investigate even higher doses going forward. We expect topline results from our Phase 1b trial in the second half of this year.”

Dapiglutide was assessed to be safe and well-tolerated in the DREAM trial. The most common treatment-emergent adverse events were related to the gastrointestinal system, including reduced appetite and nausea. Overall, the number of events observed were lower than have been reported from studies of other incretin-based therapies, and none led to treatment discontinuation in this trial.

Additional detailed results on cardiovascular risk, systemic inflammatory markers, as well as data from gut biopsies, will be presented at a future scientific meeting.

About the DREAM trial

DREAM (ClinicalTrials.gov ID: NCT05788601) is a mechanistic investigator-led, randomized, placebo-controlled, parallel-group, single-center clinical trial. In total, 54 participants with obesity (eligible BMI ≥ 30 kg/m²; median BMI in the trial was 34.8 kg/m²) were randomized to once-weekly subcutaneous treatment with either dapiglutide 4 mg, dapiglutide 6 mg or placebo. Participants on 4 mg dapiglutide were initiated at 2 mg and up-titrated after three weeks to 4 mg for the remaining nine weeks of treatment, whereas participants on 6 mg dapiglutide were initiated at 2 mg, up-titrated to 4 mg after three weeks and again after six weeks to 6 mg for the remaining six weeks of treatment (12 weeks in total).

About obesity and low-grade inflammation

Obesity is a chronic disease that results in substantial global morbidity and mortality. Excess fat storage associated with obesity can trigger low-grade systemic inflammation through reduced intestinal barrier integrity, or “leaky gut”. Obesity-related low-grade inflammation may result in several comorbidities, including cardiovascular disease, liver disease, and neuro-inflammation.  

About dapiglutide

Dapiglutide is a long-acting, dual GLP-1 receptor/GLP-2 receptor agonist for the potential treatment of obesity. This is a first-in-class peptide designed to leverage the weight loss effects of a potent GLP-1 agonist and address co-morbidities associated with low-grade inflammation through improved intestinal barrier function by GLP-2.

Previous Phase 1 results of dapiglutide in healthy volunteers demonstrated dose-dependent weight loss of up to 4.3% from baseline body weight after only four weeks of treatment (ClinicalTrials.gov ID: NCT04612517). Dapiglutide also delayed gastric emptying and reduced plasma glucose and insulin concentrations in a dose-dependent manner. Pharmacokinetics showed a mean half-life of 123-129 hours across the four dose cohorts, which supports once-weekly dose administration. Multiple weekly doses of dapiglutide were well-tolerated and the safety profile was as expected for GLP-1 and GLP-2 receptor agonists. These results were presented at the ADA 82nd Scientific Sessions in June 2022.

Zealand has initiated a Phase 1b 13-week randomized, double-blind, placebo-controlled, dose titration trial (ClinicalTrials.gov ID: NCT06000891) to evaluate significantly higher doses of dapiglutide in overweight or obese but otherwise healthy people (eligible BMI 27.0–39.9). Topline results are expected in the second half of 2024.

About Zealand Pharma

Zealand Pharma A/S (Nasdaq: ZEAL) ("Zealand") is a biotechnology company focused on the discovery and development of peptide-based medicines. More than 10 drug candidates invented by Zealand 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 was founded in 1998 and is headquartered in Copenhagen, Denmark, with a presence in the U.S. For more information about Zealand, please visit www.zealandpharma.com.

Forward-looking statements
This company announcement contains forward-looking statements that provide Zealand Pharma’s expectations or forecasts of future events regarding the research, development and commercialization of pharmaceutical products. These forward-looking statements may be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would” and other words and terms of similar meaning. You should not place undue reliance on these statements, or the scientific data presented. The reader is cautioned not to rely on these forward-looking statements. Such forward-looking statements are subject to risks, uncertainties and inaccurate assumptions, which may cause actual results to differ materially from expectations set forth herein and may cause any or all of such forward-looking statements to be incorrect, and which include, but are not limited to, the occurrence of adverse safety events; risks of unexpected costs or delays; unexpected concerns that may arise from additional data, analysis or results obtained during clinical trials; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates or expansion of product labelling; failure to obtain regulatory approvals in other jurisdictions; and product liability claims. If any or all of such forward-looking statements prove to be incorrect, our actual results could differ materially and adversely from those anticipated or implied by such statements. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. All such forward-looking statements speak only as of the date of this company announcement and are based on information available to Zealand Pharma as of the date of this announcement. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. Information concerning pharmaceuticals (including compounds under development) contained within this material is not intended as advertising or medical advice.

¹Based on the efficacy estimand: treatment effect if everyone in the target population had completed the treatments.

Contacts:

Adam Lange (Investors)
Investor Relations Officer
Zealand Pharma
[email protected]

Anna Krassowska (Investors and Media)
Vice President, Investor Relations & Corporate Communications
Zealand Pharma
[email protected]