Novo Nordisk and Septerna forge $2.2bn GPCR deal to develop oral therapies for obesity and diabetes

Novo Nordisk partners with Septerna in a $2.2B deal to develop oral GPCR therapies for obesity and diabetes. Explore the full stock sentiment and deal impact.

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How Is Novo Nordisk Partnering with Septerna to Redefine Obesity and Diabetes Treatments?

In a move poised to reshape the treatment landscape for obesity and type 2 diabetes, A/S and , Inc. have entered into a global collaboration and licensing agreement valued at approximately $2.2 billion. Announced on May 14, 2025, the strategic partnership aims to advance multiple oral small molecule therapies by leveraging Septerna’s proprietary G protein-coupled receptor (GPCR) drug discovery platform in tandem with Novo Nordisk’s scientific and commercial expertise in cardiometabolic diseases.

The deal positions both companies to capitalise on the growing demand for orally delivered treatments that offer convenience, scalability, and improved patient adherence, particularly for chronic metabolic disorders. Initial development will begin with four research programs targeting validated GPCR pathways—specifically GLP-1, GIP, and glucagon receptors—well-known for their roles in energy balance and glucose metabolism.

What Are the Strategic Objectives Behind This GPCR Collaboration?

GPCRs, the most prolific class of membrane receptors in the human body, regulate a wide range of physiological functions. They are the target of approximately one-third of all -approved drugs. Yet, more than 75% of GPCRs remain pharmaceutically untapped, representing a vast frontier for future therapeutic innovation.

Novo Nordisk’s executive vice president and chief scientific officer, Marcus Schindler, described the collaboration as an effort to expand the company’s modality options beyond peptides and into small molecules. This diversification, he noted, allows for targeting a broader range of biological pathways, flexible dosing regimens, and enhanced scalability for global distribution.

Septerna, headquartered in and listed on the Nasdaq under the ticker SEPN, has developed a proprietary Native Complex Platform that enables the isolation and reconstitution of GPCRs in a cell-free, structurally native format. This innovation allows for the identification of drug candidates that can act as agonists, antagonists, or allosteric modulators to finely tune receptor activity with a high degree of specificity.

According to Septerna’s co-founder and CEO Dr. Jeffrey Finer, Novo Nordisk’s longstanding leadership in the metabolic space makes them an ideal collaborator. He noted that the agreement provides critical operational flexibility and capital for Septerna to simultaneously pursue its broader portfolio of GPCR-targeted assets in endocrinology, immunology, and inflammation.

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What Are the Financial Terms and Development Milestones?

Septerna stands to receive approximately $2.2 billion under the terms of the agreement, which includes more than $200 million in upfront and near-term milestone payments. The company is also eligible for substantial development, regulatory, and commercial milestone payments, along with tiered royalties on net global sales of any approved therapies emerging from the collaboration.

Novo Nordisk will assume all research and development expenses across the partnered programs. Research will be conducted jointly through the lead candidate selection stage. From the IND-enabling phase onward, Novo Nordisk will take over full responsibility for global development, regulatory filings, and commercial launch.

Septerna has retained the right to opt into a global profit-sharing arrangement for one program—trading future milestones and royalties for shared revenues—an unusual but flexible feature in biotech licensing deals.

The agreement is subject to closing conditions, including the expiration of the Hart-Scott-Rodino Antitrust Improvements Act waiting period, with final execution expected by the end of Q2 2025.

What Makes Septerna’s Native Complex Platform Distinctive?

The Native Complex Platform is the cornerstone of Septerna’s approach to GPCR drug discovery. It mimics the natural cell membrane environment by assembling purified GPCRs with lipid bilayers, ligands, and associated signaling proteins in a stable, functional format outside the cell. This approach significantly improves the reliability of biochemical assays and allows for deeper exploration of ligand binding sites.

With this platform, Septerna can screen billions of small molecule compounds for interactions with difficult-to-drug or previously inaccessible GPCR targets. The platform’s modularity also supports the pursuit of differentiated pharmacology, including biased agonism, dual receptor targeting, and activity modulation via allosteric sites.

By enabling scalable small molecule design, the platform helps avoid the limitations of peptide-based biologics—particularly cost of production, storage, and administration route. This is particularly relevant for chronic disease states like obesity and diabetes, where patient convenience and global distribution are critical.

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Why Is Oral Delivery Becoming a Priority in Metabolic Therapies?

Current GLP-1 receptor agonists such as Ozempic (semaglutide) and Wegovy have transformed the treatment of obesity and type 2 diabetes but are injectable therapies, posing challenges in terms of patient adherence and cold-chain logistics. Novo Nordisk’s Rybelsus—the first oral GLP-1 therapy—proved the viability of oral formats in this category and opened the door for further investment in small molecule alternatives.

Oral delivery mechanisms offer a clear advantage in global scalability, especially in resource-limited settings. Small molecules are more amenable to room-temperature storage, require less infrastructure for administration, and typically exhibit more favorable pharmacokinetic profiles, such as faster absorption or longer half-life variants.

The collaboration with Septerna provides Novo Nordisk with another platform to expand its oral therapy offerings, reinforcing its commitment to broadening access and enhancing compliance in the management of metabolic disorders.

How Are Public Markets Reacting to the Announcement?

The announcement of the Novo Nordisk–Septerna deal on May 14, 2025, triggered a dramatic surge in Septerna’s stock (NASDAQ: SEPN), which closed 53% higher at $10.37. This marked one of the largest single-day gains in the company’s trading history and reflected strong investor enthusiasm around the long-term revenue potential of the partnership.

Septerna’s market cap saw a significant boost as a result, driven by expectations of substantial near-term milestone revenues, long-term royalties, and strategic validation of its proprietary GPCR platform. The stock’s price movement suggested both institutional accumulation and growing confidence from biotech-focused retail investors.

In contrast, Novo Nordisk (NYSE: NVO) experienced a more muted reaction. Its stock rose 1.7% to $66.51 on the same day, but the company remains down 24% year-to-date amid broader market volatility and increased competition in the GLP-1 space. Despite this, analysts viewed the collaboration positively, positioning it as part of a long-term diversification strategy that may insulate the company from overexposure to injectable-only therapeutics.

What Do Institutional Flows and Ownership Trends Reveal?

Septerna is overwhelmingly institutionally held, with nearly 99.29% of its outstanding shares owned by investment firms. Notable stakeholders include Third Rock Ventures VI LP, which holds more than 23% of the company. The high level of institutional backing suggests deep confidence in Septerna’s technology and management team.

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Following the announcement, there was a notable increase in trading volumes across biotech-oriented ETFs, with crossover interest from generalist funds seeking exposure to obesity and cardiometabolic innovation. The opt-in profit share clause adds another layer of long-term upside potential, increasing the deal’s attractiveness to venture and growth-oriented funds.

Novo Nordisk, which enjoys strong support from European and U.S. institutional investors alike, has maintained relatively stable institutional ownership despite recent share price fluctuations. Asset managers such as Jennison Associates LLC and GQG Partners LLC remain among the largest holders.

What Is the Current Investment Outlook for Both Companies?

Analyst consensus on Septerna has shifted from neutral to positive, particularly for long-term investors with higher risk tolerance. With significant upfront capital, milestone liquidity, and platform validation now in hand, Septerna is well-positioned to not only execute on this partnership but also advance internal programs across multiple therapeutic areas.

A “Buy” sentiment is emerging among market watchers, backed by strong fundamentals, technological differentiation, and robust financial backing from a tier-one pharmaceutical partner.

For Novo Nordisk, analysts maintain a “Hold” recommendation. While the long-term strategy is sound, the near-term performance remains constrained by macro headwinds and saturation in the GLP-1 peptide market. The success of the Septerna partnership could catalyze renewed investor confidence if IND milestones are met and oral candidates demonstrate strong preclinical profiles.


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