dapiglutide (ZP7570) / Zealand Pharma - LARVOL DELTA

Zealand Pharma announces positive topline results from 28-week Phase 1b trial with GLP-1/GLP-2 receptor dual agonist dapiglutide (GlobeNewswire) - P1b | N=84 | NCT06000891 | Sponsor: Zealand Pharma | "Zealand Pharma announces positive topline results from 28-week Phase 1b trial with GLP-1/GLP-2 receptor dual agonist dapiglutide...Body weight reductions of a mean of 11.6% after 28 weeks with dapiglutide escalated up to 26 mg, with 95% of trial participants being male, a median baseline BMI of 28.5 kg/m2, and no lifestyle modifications; Treatment with dapiglutide was assessed to be safe and well-tolerated with gastrointestinal adverse events consistent with the profile reported with other incretin-based therapies; Unique, dual mechanism, including GLP-2 activity, designed to target obesity-related comorbid conditions driven by low-grade inflammation...Detailed results from Part 1 of the Phase 1b MAD trial with dapiglutide will be presented at the American Diabetes Association’s 85th Scientific Sessions in Chicago, Illinois on June 20, 2025."

P1 data • Obesity

Safety, Tolerability, and Clinical Effects of Dapiglutide, a Once-Weekly GLP-1R/GLP-2R Agonist (ADA 2025) - "Dapiglutide treatment of up to 13 mg appeared safe and well-tolerated with an AE profile similar to other incretin-based therapies. The placebo-adjusted reductions in body weight were up to a mean of 8.3% with dapiglutide after 13 weekly doses. The half-life of dapiglutide is suitable for once-weekly dosing."

Clinical • Metabolic Disorders • Obesity

Dapiglutide for the Treatment of Obesity – A Double-Blind, Placebo-Controlled, Proof-of-Concept Study (ECO 2025) - "Dapiglutide treatment for 12 weeks was not significantly superior to placebo in reducing BW in persons living with obesity. Furthermore, the AE profile indicates that doses were at the lower end of the therapeutic range. Thus, larger and longer studies with higher doses and adjunct lifestyle intervention are warranted to assess the weight-lowering potential of dapiglutide."

Clinical • Cardiovascular • Genetic Disorders • Inflammation • Obesity

Upcoming events next 12 months (GlobeNewswire) - "In the first half of 2026, Zealand Pharma expects to report topline results from the Phase 2 ZUPREME-1 trial and complete the Phase 2 ZUPREME-2 trial with petrelintide...Zealand Pharma and Roche expect to initiate Phase 2 trials with petrelintide/CT-388 in the first half of 2026...In the second quarter of 2025, Zealand Pharma expects to announce topline results from Part 2 of the Phase 1b trial evaluating higher doses of dapiglutide over 28 weeks of treatment, with subsequent initiation of a Phase 2 trial expected in the second half of 2025. Zealand Pharma will present the results from Part 1 of the Phase 1b trial at the American Diabetes Association’s 85th Scientific Sessions in Chicago, Illinois in June 2025....Topline data from SYNCHRONIZE-1 and SYNCHRONIZE-2, the Phase 3 trials with survodutide in participants with overweight or obesity without and with type 2 diabetes, respectively, are expected in the first half of 2026."

Clinical data • New P2 trial • Trial status • Obesity • Type 2 Diabetes Mellitus

A Trial Comparing Pharmacokinetics, Safety and Tolerability of Two Subcutaneous Concentrations of Dapiglutide (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Zealand Pharma | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Obesity

A Trial Comparing Pharmacokinetics, Safety and Tolerability of Two Subcutaneous Concentrations of Dapiglutide (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Zealand Pharma | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

A Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZP7570 (clinicaltrials.gov) - P1 | N=84 | Terminated | Sponsor: Zealand Pharma | Recruiting ➔ Terminated; Decision by Sponsor, LSLV is planned for 21-Mar-2025.

Trial termination • Genetic Disorders • Obesity

Highlights of the year and key events anticipated in 2025 (GlobeNewswire) - "Dapiglutide, a first-in-class GLP-1/GLP-2 receptor dual agonist. Zealand Pharma reported positive topline results from the 13-week Phase 1b trial with dapiglutide, providing support for advancing this candidate into a large Phase 2b trial in people with overweight or obesity, which is planned for initiation in the first half of 2025. The company also expanded the Phase 1b trial to evaluate higher doses of dapiglutide over a longer treatment period, with topline results from this part of the trial expected in the first half of 2025."

New P2b trial • P1 data • Trial status • Obesity

A Trial Comparing Pharmacokinetics, Safety and Tolerability of Two Subcutaneous Concentrations of Dapiglutide (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Zealand Pharma

New P1 trial • Genetic Disorders • Obesity

DREAM: Dapiglutide for the Treatment of Obesity (clinicaltrials.gov) - P2 | N=54 | Active, not recruiting | Sponsor: University Hospital, Gentofte, Copenhagen | Trial completion date: Aug 2024 ➔ Aug 2025

Trial completion date • Genetic Disorders • Inflammation • Obesity

Dapiglutide for Obesity – A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Study (OBESITY WEEK 2024) - "Dapiglutide treatment for 12 weeks was not significantly superior to placebo in reducing BW in persons living with obesity. Furthermore, the AE profile indicates that doses were at the lower end of the therapeutic range. Thus, larger and longer studies with higher doses and adjunct lifestyle intervention are warranted to assess the weight-lowering potential of dapiglutide."

Clinical • Cardiovascular • Genetic Disorders • Inflammation • Obesity

Dapiglutide for the treatment of obesity: a double-blind, placebo-controlled, proof-of-concept study (EASD 2024) - P2 | "Dapiglutide treatment for 12 weeks was not significantly superior to placebo in reducing BW in persons living with obesity. Furthermore, the AE profile indicates that doses were at the lower end of the therapeutic range. Thus, larger and longer studies with higher doses and adjunct lifestyle intervention are warranted to assess the weight-lowering potential of dapiglutide."

Clinical • Late-breaking abstract • Metabolic Disorders • Obesity

A Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZP7570 (clinicaltrials.gov) - P1 | N=84 | Recruiting | Sponsor: Zealand Pharma | Trial completion date: Nov 2024 ➔ Apr 2025 | Trial primary completion date: Nov 2024 ➔ Apr 2025

Trial completion date • Trial primary completion date • Genetic Disorders • Obesity

Dapiglutide Is a Dual Agonist on Human GLP-1- and GLP-2-Receptors with a Biased and Prolonged Signaling Profile at the GLP-1R (ADA 2024) - "The human GLP-1R in vitro signaling profile was investigated in a kinetic cAMP formation assay and for recruitment of β-arrestin in HEK293 cells.Initial in vitro characterization indicated that dapiglutide is more potent for binding to GLP-1R over GLP-2R, with estimated binding affinities of 38 nM and 102 nM, respectively.​ At the GLP-1R, dapiglutide showed signaling bias, displaying full agonist activity in cAMP formation, whilst having significantly blunted response to β-arrestin recruitment. Further in vitro characterization showed that dapiglutide-induced cAMP formation kinetics persisted for up to 12 hours unlike native GLP-1, potentially reflecting signal bias, lack of receptor desensitization, and a promising efficacy profile in the MAD trial.Dapiglutide, a dual GLP-1/GLP-2 agonist, has a unique GLP-1R biased agonism signaling profile that combined with additional GLP-2R activity may translate into an efficacious weight management therapy in individuals with obesity."

Metabolic Disorders • Obesity

Zealand Pharma Announces Financial Results for the First Quarter of 2024 (GlobeNewswire) - "Dapiglutide, a GLP-1/GLP-2 receptor dual agonist. In the second quarter of 2024, Zealand anticipates topline results from the investigator-led DREAM trial that aims to evaluate the potential for weight loss following 12 weeks of treatment and gain key mechanistic insights into the effects of dapiglutide on inflammatory markers. In the second half of 2024, Zealand expects topline results from the 13-week dose titration trial..."

P1 data • P2 data • Metabolic Disorders • Obesity

A Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZP7570 (clinicaltrials.gov) - P1 | N=84 | Recruiting | Sponsor: Zealand Pharma | N=54 ➔ 84 | Trial completion date: Jul 2024 ➔ Nov 2024 | Trial primary completion date: Jul 2024 ➔ Nov 2024

Enrollment change • Trial completion date • Trial primary completion date • Genetic Disorders • Obesity

DREAM: Dapiglutide for the Treatment of Obesity (clinicaltrials.gov) - P2 | N=54 | Active, not recruiting | Sponsor: University Hospital, Gentofte, Copenhagen | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Inflammation • Obesity

Zealand Pharma Announces Financial Results for the First Nine Months of 2023 (GlobeNewswire) - "Zealand Pharma A/S...today announced the interim report for the nine months ended September 30, 2023, and provided a corporate update...In the fourth quarter of 2023, Zealand expects to submit an NDA to the FDA for glepaglutide administered via autoinjector for the treatment of short bowel syndrome with intestinal failure and subsequently engage in more detailed partnership discussions....In the first half of 2024, Zealand anticipates topline results from the ongoing investigator-led DREAM trial that aims to evaluate the potential for weight loss following 12 weeks of treatment and gain key mechanistic insights into the effects of dapiglutide on inflammatory markers. In the second half of 2024, Zealand expects topline results from the 13-week dose titration trial."

NDA • P2 data • Gastroenterology • Gastrointestinal Disorder • Metabolic Disorders • Obesity • Short Bowel Syndrome

A Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZP7570 (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Zealand Pharma | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Obesity

A Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZP7570 (clinicaltrials.gov) - P1 | N=54 | Not yet recruiting | Sponsor: Zealand Pharma

New P1 trial • Genetic Disorders • Obesity

Zealand Pharma Announces Financial Results for the First Half of 2023 (GlobeNewswire) - "Zealand expects the trial to complete in the first half of 2024...Survodutide in obesity. Boehringer Ingelheim expects to start enrolment of patients in the Phase 3 clinical program with survodutide in people living with overweight or obesity in the second half of 2023, with details on the trials to be disclosed prior to their initiation...Boehringer Ingelheim and Zealand Pharma expect to report topline results from the Phase 2 trial with survodutide in NASH in the first half of 2024....Dapiglutide, GLP-1/GLP-2 receptor dual agonist. Zealand expects to initiate a 13-week dose titration trial in people with obesity in the second half of 2023. Topline results from the ongoing investigator-initiated Phase 2 trial DREAM are expected in the first half of 2024."

Enrollment status • P2 data • Trial completion date • Immunology • Inflammation • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity

DREAM: Dapiglutide for the Treatment of Obesity (clinicaltrials.gov) - P2 | N=54 | Recruiting | Sponsor: University Hospital, Gentofte, Copenhagen | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Inflammation • Obesity • IL6 • LBP

Zealand Pharma announces directed issue and private placement of approximately 6.5 million new shares (GlobeNewswire) - "Zealand Pharma A/S...announces the launch of an offering of new shares at market price (the 'Offering'). The Offering will be completed through an accelerated bookbuilding process and will consist of approx. 6.5 million new shares (the 'New Shares') in a private placement directed at institutional and professional investors in Denmark and certain other jurisdictions....The net proceeds from the Offering are (in the following prioritized order) intended to:...Advance the clinical-stage candidates, including the obesity/metabolic disease portfolio that includes the clinical-stage GLP-1/GLP-2 dual agonist (dapiglutide) and amylin analog (ZP8396); and non-clinical stage GIP analog (ZP6590)."

Commercial • Immunology • Metabolic Disorders • Short Bowel Syndrome

DREAM: Dapiglutide for the Treatment of Obesity (clinicaltrials.gov) - P2 | N=54 | Not yet recruiting | Sponsor: University Hospital, Gentofte, Copenhagen

New P2 trial • Genetic Disorders • Inflammation • Obesity • IL6 • LBP

The dual GLP-1 and GLP-2 receptor agonist dapiglutide promotes barrier function in murine short bowel. (PubMed, Ann N Y Acad Sci) - "In the colon, dapiglutide attenuated the short bowel-associated, compensatorily increased epithelial sodium channel activity, likely secondary, by improved volume status. Future studies are needed to address the intestinal adaptation of the colon."

Biomarker • Clinical • Journal • Preclinical • Retrospective data • Review • Gastrointestinal Disorder • Short Bowel Syndrome