Zealand seeks deals in obesity and beyond
With Boehringer locked in, the Danish biotech wants more partners for monotherapies, combos and more.
Oncology remains the hottest area in pharmaceutical research – but obesity is gaining on it. Last month Boehringer Ingelheim became the latest group to push into pivotal trials in the metabolic disease with BI 456906. The good news for other companies wishing to move into this area is that the originator of that project, Zealand Pharma, has several more obesity assets for which it is eagerly seeking partners.
“We want to refocus our efforts on what we are best at, and that is peptide drug discovery and development,” says Zealand’s chief executive, Adam Steensberg.
BI 456906 is a GLP-1/glucagon dual agonist – a fairly common mechanistic approach to obesity. This class was knocked, however, when Altimmune reported data on pemvidutide showing decent efficacy, but worryingly high rates of side effect-driven discontinuations.
BI 456906 will not disappoint in this way, says Steensberg. While it hits the same targets as pemvidutide it hits them in different proportions, he says: BI 456906 has eightfold greater affinity for the GLP-1 receptor than the glucagon receptor, where pemvidutide is equimolar.
“It’s a design principle for all our dual-acting peptides that we really want to make sure that we harvest the known benefits GLP-1, and then we just add a little bit more pharmacology,” Steensberg says.
This principle also applies to dapiglutide, one of Zealand’s unpartnered obesity assets and a project with the unusual mechanism of dual GLP-1 and GLP-2 agonism. It skews heavily toward activity at the GLP-1 receptor, Steensberg says.
Adding GLP-2 agonism to GLP-1 is intended to have a dual function. GLP-2 has a role in intestinal permeability, and research suggests that some obese individuals have an impaired intestinal barrier; bacteria crossing this and entering the bloodstream drive the low-grade inflammation seen in obesity, Steensberg explains. The idea with dapiglutide is to achieve the beneficial effects of a GLP-1, but also provide “a little bit of GLP-2 so we can seal the gut”, he says.
There is also reason to believe that co-administering a GLP-1 and 2 might reduce the nausea and vomiting that are common with the incretin class, he says. “We also hope that our molecule will be more tolerable than a molecule that only has GLP-1.” A phase 2 trial is to begin soon, and ought to report next year, and another trial testing higher doses is also planned.
Bucking the combo trend
The other two compounds Zealand is developing for obesity have single mechanisms – increasingly rare in the age of obesity combos. ZP8396, an amylin analogue, recently showed bodyweight reductions of up to 4.2% in a phase 1 trial, versus a gain of 0.6% seen in placebo patients.
That is promising for a single dose of a monotherapy, and Zealand is intent on pursuing monotherapy development for patients who do not benefit from, or cannot tolerate, GLP-1-containing medicines. The company believes that it could eventually achieve double-digit weight loss with ZP8396 alone. But the group also intends to position the project as an add-on to existing obesity therapies.
“Our amylin analogue … can be coformulated with all the GLP-1 molecules we know of, including Novo’s Wegovy, Lilly’s tirzepetide, Boehringer’s GLP-1/glucagon and our own GLP-1/2,” Steensberg says. This is different to Novo’s amylin, which cannot be used in the same way, as an add-on to separate GLP-1s, he says.
Should the amylin analogue reach market, then, it could form part of therapies competing with Novo’s cagrisema, a fixed-dose combination of the amylin agent cagrilintide and Wegovy. Cagrisema is in a phase 3 trial, Redefine-2, in which Novo is targeting weight loss of 25%.
Zealand’s single-action GIP agonist will also be developed as an add-on therapy, but the group does not think it has monotherapy potential.
These three unpartnered obesity assets might not remain unpartnered for long. Zealand is seeking co-development agreements, “where we play a strategic role and an active role in the partnerships, at least until we reach the commercial stage”, Steensberg says. It has had talks here, but these are “not very mature”; the group hopes to have collaborators signed up before late-stage trials start.
Following a recent fundraising Zealand has cash to last it to mid-2026. This could be bolstered by milestones from its existing partnerships with Boehringer, Alexion and Novo. The cash runway could also be extended with new collaborations, and two advanced assets outside the obesity arena are key here.
One of these is Zegalogue, which Zealand plans to sell itself in its first indication, severe hypoglycaemia, but the group is shopping for a partner for the product’s hoped-for second indication, congenital hyperinsulinism. And its GLP-2, glepaglutide, will yield more phase 3 data in short bowel syndrome next year. Steensberg confirms that the group is in talks with potential partners for both projects, with the aim being that these will take charge of commercialisation.
Deals might or might not materialise. But, by being active in rare diseases and obesity, Zealand is giving itself a good chance of finding collaborators.
|Zealand Pharma's pipeline|
|Project||Mechanism||Development status||Partnership status|
|Zegalogue (dasiglucagon) sc infusion||Glucagon analogue||Approved for severe hypoglycaemia in diabetes Mar 2021; NDA for CHI expected H1 2023||In talks for CHI partnership|
|Zegalogue (dasiglucagon) low-dose pen||Glucagon analogue||Ph2 trial in mild hypoglycaemia in type 1 diabetes completed||Novo Nordisk|
|Glepaglutide||GLP-2 analogue||Ph3 Ease SBS 1 in short bowel syndrome reported Sep 2022; Ease SBS 2 and 3 could report 2024||In talks|
|BI 456906||Glucagon/GLP-1 agonist||Ph3 in obesity imminent; ph2 in Nash could report 2023; ph2 in type 2 diabetes complete||Boehringer Ingelheim|
|Dapiglutide/ZP7570||GLP-1/GLP-2 agonist||Dream Ph2 obesity trial not yet started, could report early 2024||To be sought before ph3 trials start|
|ZP 8396||Amylin analogue||Ph1 obesity trial reported promising data Mar 2023||To be sought before ph3 trials start|
|ZP 6590||GIP agonist||Ph1 in obesity imminent||To be sought before ph3 trials start|
|Dasiglucagon (bi-hormonal artificial pancreas systems)||Glucagon analogue||Ph3 in type 1 diabetes to start 2023||Beta Bionics|
|Dasiglucagon (bi-hormonal artificial pancreas systems)||Glucagon analogue||Stable-1 Ph1 trial in type 1 diabetes not yet started, could report 2023||Inreda Diabetic|
|Unnamed||Complement C3 Inhibitor||In preclinical research for inflammation||Alexion|
|ZP 9830||Kv1.3 ion channel blocker||In preclinical research for inflammation||No immediate plans|
|ZP 10000||a4ß7 Integrin Inhibitor||In preclinical research for inflammation||No immediate plans|
|CHI=congenital hyperinsulinism. Source: Evaluate Pharma, clinicaltrials.gov & company website.|