dapiglutide (ZP7570) / Zealand Pharma - LARVOL DELTA

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

Zealand Pharma announces successful outcome of Phase 1b clinical trial with GLP1-GLP2 dual receptor agonist, dapiglutide (GlobeNewswire) - P1, N=40; NCT04612517; Sponsor: Zealand Pharma; "Zealand Pharma A/S...announces topline results from its Phase 1b multiple ascending dose trial with dapiglutide...Treatment with dapiglutide was associated with higher rates of gastrointestinal symptoms at the highest doses, with side effects being in line with what was observed in Phase 1a. No subjects withdrew from the study and overall, dapiglutide was assessed to be safe and well tolerated in the study."

P1 data • Gastrointestinal Disorder • Short Bowel Syndrome

Dapiglutide: Patent expiry in 2037 (Zealand Pharma) - Q3 2021 Results

Patent • Short Bowel Syndrome

Dapiglutide, a novel dual GLP-1 and GLP-2 receptor agonist, attenuates intestinal insufficiency in a murine model of short bowel. (PubMed, JPEN J Parenter Enteral Nutr) - "Dapiglutide possesses specific and potent GLP-1 and GLP-2 receptor agonist effects in rodents. In the murine SB model, combined unimolecular GLP-1R and GLP-2R stimulation with dapiglutide potently attenuates intestinal insufficiency and potentially also IF."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Short Bowel Syndrome

[VIRTUAL] THE NOVEL DUAL GLP-1 AND GLP-2 RECEPTOR AGONIST DAPIGLUTIDE ATTENUATES INTESTINAL INSUFFICIENCY IN A MURINE SHORT BOWEL MODEL (UEGW 2021) - "In the murine short bowel model, combined unimolecular GLP-1R and GLP-2R stimulation with dapiglutide potently attenuates intestinal insufficiency."

Preclinical

[VIRTUAL] THE NOVEL DUAL GLP-1 AND GLP-2 RECEPTOR AGONIST DAPIGLUTIDE ATTENUATES INTESTINAL INSUFFICIENCY IN A MURINE SHORT BOWEL MODEL (UEGW 2021) - "In the murine short bowel model, combined unimolecular GLP-1R and GLP-2R stimulation with dapiglutide potently attenuates intestinal insufficiency."

Preclinical

[VIRTUAL] THE NOVEL DUAL GLP-1 AND GLP-2 RECEPTOR AGONIST DAPIGLUTIDE ATTENUATES INTESTINAL INSUFFICIENCY IN A MURINE SHORT BOWEL MODEL (UEGW 2021) - "In the murine short bowel model, combined unimolecular GLP-1R and GLP-2R stimulation with dapiglutide potently attenuates intestinal insufficiency."

Preclinical

A Multiple Ascending Dose Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZP7570 (clinicaltrials.gov) - P1; N=40; Completed; Sponsor: Zealand Pharma; Active, not recruiting ➔ Completed

Clinical • Trial completion

A Multiple Ascending Dose Trial Assessing Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ZP7570 (clinicaltrials.gov) - P1; N=40; Active, not recruiting; Sponsor: Zealand Pharma; Recruiting ➔ Active, not recruiting; N=30 ➔ 40; Trial completion date: Jun 2021 ➔ Sep 2021; Trial primary completion date: May 2021 ➔ Sep 2021

Clinical • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date

Zealand Pharma: on Track for Potential First Product Launch and Establishing Commercial Operations in the United States (Yahoo Finance) - "Though COVID-19 impacted patient recruitment for the Phase 3 trial of glepaglutide in SBS, the trial continues to enroll patients....They will be treated for six months whereafter they are offered a further 2-year treatment with glepaglutide in an extension trial, EASE-SBS 2. The primary endpoint is the absolute reduction in parenteral support achieved by the end of the trial, with results expected in 2022....The Company also...initiated another Phase 1 multiple-ascending dose trial....Zealand is currently at the second dose level with results of this trial expected later this year."

Enrollment status • P1 data • P3 data • Trial status • Short Bowel Syndrome

Dapiglutide: Data from P1 trial (NCT04612517) for healthy subjects in 2021 (Zealand Pharma) - Virtual Research & Development Day

P1 data • Short Bowel Syndrome