Novo Nordisk and Septerna to develop oral small molecule medicines for obesity

Novo Nordisk and Septerna have announced an exclusive global collaboration and license agreement to discover, develop and commercialise oral small molecule medicines for obesity, type 2 diabetes and other cardiometabolic diseases.

The companies will initially commence four development programmes for potential small molecule therapies directed to one or more select G protein-coupled receptor (GPCR) targets, including the GLP-1, GIP and glucagon receptors.

GPCRs represent the largest and most diverse family of cell membrane receptors, with hundreds of different GPCRs regulating physiological processes in nearly every organ system of the human body. Using its proprietary Native Complex Platform, Septerna aims to unlock the full potential of GPCR therapies. The company is focused on the discovery and development of a pipeline of oral small molecules for multiple therapeutic areas, initially focused on endocrinology, immunology and inflammation, and metabolic diseases.

GPCRs have been the most productive target class in drug discovery history, accounting for approximately one-third of all FDA-approved drugs. However, around 75% of potential GPCR therapeutic targets remain undrugged, representing a substantial untapped opportunity for future drug discovery.

Septerna has developed proprietary technologies to isolate, purify, and reconstitute GPCRs outside of cells into complexes with ligands, transducer proteins, and lipid bilayers which mimic cell membranes. These reconstituted assemblies are called Native Complexes because they replicate the natural structure, function, and dynamics of GPCRs in purified biochemical formats.

The Native Complex Platform™ is powered by a suite of tools and technologies that allow screening of billions of candidate molecules. It is designed to target specific GPCRs, uncover novel binding pockets for validated receptors, and pursue a wide spectrum of pharmacologies, including agonists (which activate GPCR signalling), antagonists (which inhibit GPCR signalling), and allosteric modulators (which either increase or decrease the degree of GPCR activation by endogenous ligands), to affect GPCR signalling in different ways to achieve desired therapeutic effects.

Under the terms of the agreement, Septerna is eligible to receive approximately US$2.2 billion US dollars from Novo Nordisk across an upfront payment and research, development and commercial milestone payments. This includes more than US$200 million in upfront and near-term milestone payments. Septerna is also eligible to receive tiered royalties on global net sales of marketed products. Novo Nordisk will cover all research and development expenses for partnered programs under the collaboration.

The companies will jointly conduct research activities from discovery through development candidate selection. Starting at IND-enabling activities, Novo Nordisk will have sole responsibility for all global development and commercialisation activities. In addition, Septerna has the right to opt in to a worldwide profit share for one programme in the collaboration in lieu of future milestones and royalties for that product candidate.

The agreement is subject to customary closing conditions and is expected to occur in the second quarter of 2025.