Zealand Pharma sets second-half 2026 deadlines for petrelintide Phase 3 and ZUPREME-2

Zealand Pharma has said that topline results from the Phase 2 ZUPREME-2 trial of petrelintide in people with overweight or obesity and type 2 diabetes are due in the second half of 2026, and that it and Roche expect to begin registrational Phase 3 trials of petrelintide used alone in the same window ^[1][2]. The two companies also plan to start a Phase 2 trial, ZYNERGY, testing petrelintide in combination with a GLP-1/GIP dual agonist ^[1][2].

Petrelintide is an amylin analog, a different mechanism from the GLP-1 drugs sold as Ozempic, Wegovy, Rybelsus and the GLP-1/GIP drug tirzepatide (Mounjaro, Zepbound) ^[1]. It is not approved by the FDA or the EMA for chronic weight management ^[2]. In an obesity market pipeline listing, petrelintide is credited with up to 10.7% weight loss at 42 weeks, with tolerability described as placebo-like and no vomiting reported in the maximum effective dose group ^[1]. The same listing attributes roughly 21% weight loss at 72 weeks to tirzepatide and roughly 15% at 68 weeks to semaglutide; those figures come from separate trials ^[1].

ZUPREME-1, an earlier Phase 2 trial, produced double-digit weight loss with a tolerability profile largely comparable to placebo, and Zealand has said that dataset is what supports moving into late-stage testing ^[2]. The company has framed tolerability as the differentiator, in a drug class where gastrointestinal side effects often limit how far doses can be raised and whether people stay on treatment ^[2].

Roche and Zealand are partnered on petrelintide in a deal valued at up to about $5.3 billion, including $1.65 billion upfront, according to the partnership listing ^[1]. Zealand reported recognizing $700 million in collaboration revenue from Roche in the second quarter of 2026 following confirmation that petrelintide would advance ^[2]. Zealand's listed cash position is about $2.1 billion, or DKK 14.5 billion ^[1].

The company has also been returning capital while it prepares for Phase 3. It launched a $200 million share buyback in the second quarter of 2026 and struck a separate $100 million royalty monetization agreement with Royalty Pharma for the non-core asset rusfertide ^[2]. Full-year 2026 operating expenses are guided at DKK 2.7 billion to DKK 3.3 billion, driven mainly by the petrelintide program ^[2]. On September 2, Zealand filed a correction to its week 35 buyback transactions, designated Company Announcement No. 45/2026, amending data for the period ending August 28, 2026 ^[2]. The announcement did not say what specifically was corrected, and the company said the filing was procedural rather than a suspension of the buyback ^[2].

Why it matters for patients

The approved GLP-1 and GLP-1/GIP drugs work well for many people, but side effects including nausea and vomiting are a common reason people lower their dose or stop ^[2]. Petrelintide is being developed on the theory that a drug with less of that burden can be useful even if it does not produce the largest weight loss on the market ^[1][2]. If the tolerability signal holds in larger trials, it could matter most for people who have struggled to stay on a GLP-1 drug — though no approved amylin drug for weight management currently exists in the US ^[1][2].

The combination approach cuts both ways for patients: pairing an amylin drug with a GLP-1/GIP agonist could add efficacy, but it also reintroduces the GLP-1 side effects the monotherapy is trying to avoid ^[1][2]. Nothing in the disclosures addresses cost, insurance coverage or how petrelintide would compare head-to-head with approved medicines; those have not been reported ^[1][2].

What happens next

Three events are guided to the second half of 2026: ZUPREME-2 topline results in overweight or obesity with type 2 diabetes, the start of registrational Phase 3 trials of petrelintide monotherapy, and the start of the Phase 2 ZYNERGY combination trial ^[1][2]. The Phase 3 program's design, sample size and primary endpoints have not been detailed in public filings ^[2].

One detail is unresolved across accounts: the GLP-1/GIP dual agonist named as petrelintide's combination partner in ZYNERGY is called enicepatide in one ^[1] and anasepatide in another ^[2]. The naming has not been reconciled.