COPENHAGEN (Reuters) -Novo Nordisk has struck a collaboration and licensing deal with U.S. biotech Septerna to develop oral small molecule medicines for obesity, type 2 diabetes and other cardio-metabolic diseases that could be worth up to $2.2 billion for Septerna, they said on Wednesday.

Novo, maker of the wildly popular Wegovy weight-loss drug, has sought to further strengthen its position in the potential $150 billion obesity market through the development of next-generation drugs, acquisitions and partnerships.

Investors have been concerned that Novo's first-to-market drug is losing its lead to Eli Lilly, whose U.S. prescriptions for its Zepbound obesity shot have surpassed Wegovy since mid-March.

"Novo Nordisk has a rich history of innovation in obesity and diabetes," the Danish company's Chief Scientific Officer Marcus Schindler said in a statement.

"We are building on our scientific leadership in this space and developing a broad pipeline across various targets and modalities, including peptides and small molecules," he said.

The new partnership includes more than $200 million in upfront and near-term payments for Septerna, the companies said.

California-based Septerna is developing therapies targeting G-protein-coupled receptors (GPCR), a class of proteins that serve as a main conduit for chemicals to get past a cell's membrane and be taken up by a cell.

GPCR can influence broad physiological processes such as metabolism, secretion, cell growth, and immune responses.

The two companies aim to commence four development programmes for potential small molecule therapies directed at select GPCR targets.

The collaboration is the second significant pharma deal in obesity in as many months. In March, Roche said it would pay up to $5.3 billion to co-develop and co-commercialise Zealand Pharma's obesity drug candidate.

Separately, U.S. regulators this month accepted Novo's submission for an oral version of Wegovy which, if approved, would become the first oral therapy for obesity from the GLP-1 drug class to which both it and Zepbound belong.

Goldman Sachs owns a 3.3% stake in Septerna, while healthcare-focused venture capital firm Third Rock Ventures holds 23.7%, according to LSEG data.

(Reporting by Stine JacobsenEditing by Mark Potter)