Zealand Pharma sets second-half deadlines for petrelintide Phase 3 and ZUPREME-2

Zealand Pharma used its half-year report to put dates on the next steps for petrelintide, an experimental once-weekly amylin analog it is developing with Roche. Topline results from the Phase 2 ZUPREME-2 trial, which tests petrelintide in people with overweight or obesity who also have type 2 diabetes, are scheduled for the second half of 2026 ^[2]. The two companies also confirmed they will begin registrational Phase 3 trials of petrelintide as a standalone treatment in the same window ^[2].

The decision to move into Phase 3 rests on the completed Phase 2 ZUPREME-1 trial, which showed double-digit weight loss with a tolerability profile the company describes as largely comparable to placebo ^[2]. Trackers of the obesity pipeline put that Phase 2 result at up to 10.7% weight loss over 42 weeks, with no vomiting reported in the group on the highest effective dose ^[1]. That is the core of the petrelintide argument: not the biggest number on the scoreboard, but side effects close to what patients on placebo experience ^[1].

For context, the drugs ahead of it in development report larger reductions. Eli Lilly's retatrutide showed 28.3% weight loss at 80 weeks in TRIUMPH-1, Novo Nordisk's CagriSema about 22.7%, Amgen's MariTide up to about 20% at 52 weeks, tirzepatide about 21% at 72 weeks and semaglutide about 15% at 68 weeks ^[1]. Petrelintide works through amylin, a different hormone pathway than the GLP-1 and GIP receptors targeted by most approved obesity drugs ^[1].

The third piece of the plan is a combination. Zealand and Roche intend to start the Phase 2 ZYNERGY trial pairing petrelintide with a GLP-1/GIP dual agonist ^[2]. The sources name that partner molecule differently: one report calls it anasepatide ^[2], while an industry catalyst calendar lists the same combination trial as petrelintide plus enicepatide ^[1]. The discrepancy is not resolved in the available material.

Money is not the constraint here. Zealand's partnership with Roche is worth up to $5.3 billion, with $1.65 billion paid upfront ^[1], and the company reported recognizing $700 million in collaboration revenue from Roche in the second quarter after petrelintide's progression was confirmed ^[2]. Cash stands at roughly $2.1 billion (DKK 14.5 billion) ^[1], and full-year 2026 operating expenses are guided at DKK 2.7 billion to DKK 3.3 billion, driven mainly by the petrelintide program ^[2]. The company is also running a $200 million share buyback launched in the second quarter of 2026 ^[2].

Why it matters for patients

Gastrointestinal side effects are the most common reason people struggle to raise their dose or stay on GLP-1 medicines, and they frequently limit how far a dose can be titrated ^[2]. A drug that delivers roughly 10% weight loss with placebo-like tolerability ^[1] would be a different kind of option than one that delivers 20% or more but comes with nausea and vomiting. Whether that trade-off appeals will depend on the individual, and the Phase 3 program is designed to test it in a larger, regulated setting.

ZUPREME-2 also matters because type 2 diabetes changes the math. Weight loss with incretin drugs is generally smaller in people with type 2 diabetes than in people without it, so the ZUPREME-2 readout will be the first look at how petrelintide performs in that group.

Several key details are not yet public. The design, sample size and primary endpoints of the Phase 3 monotherapy program have not been disclosed beyond the H2 2026 start window ^[2]. Petrelintide is investigational and is not approved by the FDA or EMA for chronic weight management ^[2]. No approval date has been announced, and Phase 3 obesity trials typically run well over a year before topline data.

What happens next

• Second half of 2026: ZUPREME-2 topline results in overweight or obesity with type 2 diabetes ^[2].
• Second half of 2026: start of registrational Phase 3 trials of petrelintide monotherapy ^[2].
• Second half of 2026: planned start of the Phase 2 ZYNERGY combination trial ^[1][2].
• Second half of 2026: an FDA decision on Novo Nordisk's CagriSema, the first once-weekly GLP-1 plus amylin combination filed for weight management, which would be the first regulatory test of the amylin approach ^[1].