Deep Apple Therapeutics signs $812m global deal with Novo Nordisk for oral cardiometabolic drugs

Why Novo Nordisk is investing in AI-powered oral drugs for obesity and metabolic diseases

Deep Apple Therapeutics, a structure-guided drug discovery startup backed by Apple Tree Partners, announced a research collaboration and licensing agreement with Novo Nordisk on June 11, 2025, focused on advancing oral small molecule therapeutics for cardiometabolic diseases. The partnership aims to exploit a novel non-incretin G-protein coupled receptor (GPCR) target with the goal of delivering first-in-class therapies for obesity and related metabolic disorders.

The American biotech company will use its proprietary AI-enabled platform to discover and optimize candidate molecules during the early phase of the program. Novo Nordisk will take over preclinical development from the IND-enabling stage and will lead global manufacturing and commercialization efforts. In return, Deep Apple Therapeutics is eligible to receive up to $812 million, comprising upfront payments, research cost reimbursements, milestone-based development payments, and tiered royalties on net product sales.

The partnership adds further momentum to Novo Nordisk’s efforts to expand its obesity portfolio beyond incretin-based therapies like semaglutide and reinforces the industry’s increasing reliance on AI-first platforms for identifying next-generation small molecules.

How GPCR targets offer a new path beyond GLP-1 in obesity and cardiometabolic treatment

Novo Nordisk’s dominant position in the global metabolic disease landscape is anchored by its GLP-1 receptor agonist franchise, including Ozempic, Wegovy, and the oral formulation Rybelsus. These drugs have revolutionized obesity and diabetes treatment, but they are not without limitations. Injectable administration, gastrointestinal side effects, and contraindications for specific populations have spurred the search for alternative pathways.

Deep Apple Therapeutics, founded to tackle undruggable protein targets through ensemble cryo-electron microscopy (cryo-EM) and AI-guided virtual screening, has identified a promising non-incretin GPCR that could modulate key metabolic pathways through a completely novel mechanism. If successful, such compounds could represent a new therapeutic class that offers oral convenience, differentiated efficacy, and improved tolerability.

This marks one of the first publicly announced collaborations involving Deep Apple Therapeutics and provides a real-world test of its Orchard.ai platform, which combines conformational ensemble data with machine learning to unlock cryptic druggable pockets in protein structures.

What this partnership signals about Novo Nordisk’s drug discovery roadmap

Novo Nordisk’s senior leadership emphasized the company’s continued interest in diversifying its cardiometabolic drug pipeline through different modalities and mechanisms. Jacob Sten Petersen, who leads the diabetes, obesity, and MASH therapeutic division, noted that the Deep Apple alliance aligns with Novo Nordisk’s goal to meet diverse patient needs and preferences, particularly in delivering effective oral medications.

Industry analysts have interpreted the collaboration as a calculated move to de-risk early-stage innovation through external partnerships. While Novo Nordisk brings late-stage development and commercial muscle, Deep Apple’s AI-native discovery approach could offer speed and novelty not readily achievable through traditional screening.

The collaboration follows similar trends observed in recent Novo Nordisk deals, including its acquisitions of Inversago Pharma and Embark Biotech, both of which added differentiated oral assets to the cardiometabolic pipeline. However, unlike those deals, the Deep Apple agreement is rooted in joint early-stage discovery rather than asset-based acquisition.

How Deep Apple could earn up to $812 million through the Novo Nordisk agreement

The deal structure reflects a standard discovery-stage biotech licensing framework with performance-linked economics. Deep Apple Therapeutics will receive an undisclosed upfront payment and full reimbursement of research-related costs as it applies its platform to the selected GPCR target.

Upon successful transfer of optimized candidates into the IND-enabling phase, Novo Nordisk will assume responsibility for all development activities. As the program progresses through preclinical and clinical milestones, Deep Apple could receive additional success-based payments, pushing the total deal value up to $812 million.

If commercialized, Deep Apple will earn royalties on global sales, likely in a low- to mid-single-digit percentage range, depending on tiered sales thresholds. While such licensing economics are typical for AI-native biotech platforms, the deal’s magnitude suggests confidence in both the platform and the target’s therapeutic relevance.

What makes Deep Apple’s platform different from traditional discovery methods

Deep Apple Therapeutics differentiates itself by leveraging structural biology in motion. Its platform captures GPCRs and other dynamic proteins in multiple conformational states using ensemble cryo-EM—a technique that allows for the visualization of moving, flexible receptors rather than just static snapshots.

This dynamic mapping is then integrated with a proprietary virtual library of multi-billion compound structures generated using the Orchard.ai algorithm. By simulating the interaction between ligands and receptors across a spectrum of molecular conformations, Deep Apple aims to uncover cryptic binding pockets that are not visible in traditional X-ray crystallography or single-conformation cryo-EM studies.

This approach is especially powerful for drugging GPCRs, which are structurally complex and notoriously difficult targets for small molecules. The ability to dock libraries against transient conformations opens the possibility of discovering entirely new classes of ligands that were previously inaccessible.

What the Deep Apple–Novo Nordisk deal means for AI-first biotech platforms

The partnership offers strategic upside to both parties. For Novo Nordisk, it brings a new target class into its development portfolio and supports its strategic narrative around innovation leadership in cardiometabolic diseases. For investors tracking Novo Nordisk, this adds to a recent streak of aggressive pipeline expansion moves following record-breaking revenues from Wegovy and Rybelsus.

For Deep Apple, the deal validates its drug discovery platform, offers early non-dilutive capital, and provides global exposure through alignment with one of the world’s most successful metabolic drug developers. Backers such as Apple Tree Partners are likely to view this collaboration as a critical inflection point for potential future financing or strategic options.

Institutional analysts tracking platform-driven drug discovery firms will likely compare this deal with those involving companies like Structure Therapeutics, Insitro, Recursion Pharmaceuticals, or Relay Therapeutics—all of which have attempted to marry AI and structural biology into scalable drug development engines.

Why GPCR drug discovery is regaining momentum in the cardiometabolic space

The renewed interest in GPCRs within cardiometabolic diseases is part of a broader biopharma trend. These membrane-bound proteins govern a wide range of physiological processes but have historically been overlooked due to discovery challenges. Recent advances in structural resolution, high-throughput docking, and AI-driven simulation are beginning to reverse that trend.

Companies like Septerna and Structure Therapeutics have also focused on GPCRs using novel discovery platforms. Deep Apple’s differentiation lies in its dynamic structural modeling, which could give it an edge in tackling difficult-to-drug receptors with greater speed and accuracy.

Novo Nordisk’s support of this direction suggests the pharmaceutical major sees long-term promise in GPCRs as a modality—not just for glucose control or appetite suppression, but also for broader homeostatic regulation, lipid metabolism, and inflammation.

What comes next for Deep Apple’s GPCR program after the Novo Nordisk handoff

The immediate next step in the collaboration involves Deep Apple Therapeutics applying its platform to generate and optimize lead compounds against the selected GPCR target. This discovery phase, expected to span roughly 12 to 18 months, will culminate in the transfer of development-ready candidates to Novo Nordisk for IND-enabling studies and eventual clinical trials.

Should the program advance to clinical validation, it could open the door to more expansive collaborations between the two firms and further establish Deep Apple’s platform as a credible engine for oral drug discovery. Novo Nordisk, for its part, could gain a competitive edge in offering novel oral treatments that address unmet needs in the rapidly evolving cardiometabolic landscape.

As regulatory agencies increasingly prioritize innovation and patient-centricity in obesity and metabolic drug development, the partnership stands to benefit from supportive frameworks, expedited designations, and payer interest in differentiated oral assets.

A structurally bold step toward next-generation metabolic therapies

The $812 million partnership between Deep Apple Therapeutics and Novo Nordisk is more than just a transaction—it represents a shift in how small molecule drugs may be discovered and developed in the era of AI and structural precision. By targeting a non-incretin GPCR with oral therapeutics, the partners are betting on novel biology, platform speed, and global market demand for alternatives to injectables.

Whether this results in the next blockbuster remains to be seen, but it undoubtedly pushes the boundaries of what’s possible in GPCR-targeted cardiometabolic innovation. With Novo Nordisk’s strategic weight behind it, Deep Apple now has a high-visibility runway to demonstrate what AI-native drug discovery can truly achieve.