In what it says is the biggest obesity deal to date, Zealand Pharma A/S has signed up Roche AG to a potential $5.3 billion global collaboration and license agreement to develop petrelintide, an amylin analog that is currently in phase IIb development.

The two companies will co-develop and co-commercialize petrelintide and combination products, including a fixed-dose combination of petrelintide and CT-388, Roche’s dual GLP-1/GIP receptor dual agonist.

“We are extremely happy with the agreement, and not least, the opportunity to collaborate with Roche, to bring petrelintide forwards as a future foundational therapy – we could not be more excited,” Adam Steensberg, president and CEO of Zealand Pharma told BioWorld.

Money apart, the attractions include Roche’s global manufacturing network and commercial reach, and a complementary portfolio of clinical programs in obesity. “We consider Roche the ideal partner,” Steensberg said. 

“[Petrelintide] holds potential to address unmet medical needs among the majority of people living with overweight and obesity, both as stand-alone therapy and in combination with other agents. This collaboration with Roche is a step change to realize this vision, while solidifying Zealand Pharma as a key player in the future management of obesity,” said Steensberg.

Copenhagen, Denmark-based Zealand and Roche will co-develop and co-commercialize petrelintide, and potential combination products, in the U.S. and Europe, with Roche having exclusive rights to commercialization in the rest of the world. 

Zealand Pharma can participate in up to 50% of commercialization activities in the U.S. and Europe but will be able to opt out and opt in under certain pre-agreed conditions. Roche will be responsible for commercial manufacturing, including the capital investment in manufacturing facilities.

 Zealand is in line for up-front cash payments of $1.65 billion, with $1.4 billion due upon closing and $250 million over the first two anniversaries of the collaboration. 

Following this are development milestones of $1.2 billion, which are mainly tied to the start of phase III trials of petrelintide as a monotherapy, plus sales-based milestones of $2.4 billion. 

Profits and losses for petrelintide and the petrelintide/CT-388 combination will be shared on a 50:50 basis in the U.S. and Europe, while Zealand will be eligible to receive tiered double-digit royalties up to high teens on net sales in the rest of the world.

Zealand will pay Roche $350 million, which will be offset against development milestone payments, for the petrelintide/CT-388 fixed-dose combination product and other petrelintide combination products.

Petrelintide is a long-acting amylin analog administered once-weekly by subcutaneous injection. Amylin receptor activation has been shown to reduce body weight by restoring sensitivity to the satiety hormone leptin, inducing a sense of feeling full faster. Current clinical or preclinical data suggest petrelintide has the potential to promote weight loss comparable to GLP-1 receptor agonists, but with improved tolerability.

In the phase Ib multiple ascending dose trial, petrelintide delivered weight reductions of up to a mean of 8.6% after 16 weeks, versus 1.7% for placebo. The drug was well tolerated, with no serious or severe adverse events. It is now in the phase IIb ZUPREME-1 trial for people with obesity/overweight without type II diabetes, which started in December 2024. ZUPREME-2 is for people with obesity/overweight with type II diabetes is due to start in the first half of 2025.

Editor’s note: This story will be updated later today.