Skape Bio Launches Nature-Published Platform for AI-Designed GPCR Biotherapeutics

• Nature study describes a de novo protein design and high-throughput living-cell screening platform for creating miniproteins that modulate G protein-coupled receptors (GPCRs), a major class of drug targets.

• The study produced functional lead molecules against 11 GPCR targets, including receptors involved in cancer, diabetes, obesity, migraine, itch, and pain.

• The work lays the foundation for Skape’s platform to develop therapeutics against hard-to-target GPCRs, with Nobel laureate David Baker and colleagues at the University of Washington’s Institute for Protein Design.

COPENHAGEN, Denmark--(BUSINESS WIRE)--Skape Bio and researchers at the University of Washington’s Institute for Protein Design (IPD) today announced a peer-reviewed study published in the leading international journal Nature demonstrating a new way to design protein-based medicines for G protein-coupled receptors, or GPCRs, one of the most important classes of drug targets in medicine.

GPCRs are cell-surface receptors that help the body respond to signals such as hormones, neurotransmitters, and sensory molecules. They are central to many of the world’s most common diseases, and approximately one-third of approved drugs act on GPCRs. Yet despite their importance, many GPCRs remain difficult to target with biologic medicines because their function depends on flexible, membrane-embedded shapes that shift between active and inactive signaling states.

The co-led Nature study addresses that challenge by designing miniproteins from scratch to recognize and stabilize specific GPCR states. Using computational protein design, the team created molecules that could either activate GPCR signaling or block it, depending on the receptor state they were built to engage. Across the study, the researchers generated functional lead molecules against 11 GPCR targets, including both agonists and antagonists.

“Designing proteins that activate GPCRs requires getting the geometry of the receptor interface exactly right,” said David Baker, PhD, Nobel laureate, co-founder and board observer at Skape Bio. “The structural data confirm that we can do that reliably across multiple receptor families, expanding the range of GPCRs that can be addressed with protein-based medicines.”

A key part of the work was a new high-throughput screening system that tests designed proteins against full-length GPCRs in living human cells. The system can evaluate up to 100,000 designs while keeping the receptors in their natural membrane environment, where GPCRs signal. This overcomes a major limitation of traditional discovery approaches, which often require removing receptors from the cell membrane or screening at much lower throughput.

The study reports designed molecules that bind GPCRs associated with cancer, metabolic disease, migraine, itch, and pain. In preclinical in vivo studies, one designed antagonist performed comparably to an existing drug while showing fewer unwanted side effects. In another example, the team extended the half-life of a receptor antagonist by attaching a commonly used protein tag, supporting dosing properties consistent with conventional therapeutics.

GPCR-targeted medicines represent one of the largest areas of modern pharmacology, with approved drugs generating more than $200 billion in annual sales. Recent GLP-1 agonists, such as Ozempic, which is widely used for weight loss, have further highlighted the therapeutic and commercial importance of the target class. However, GPCR medicines are still dominated by small molecules and peptides, which can face limitations in selectivity, durability, and safety. Protein therapeutics could offer a more precise way to control GPCR signaling, but until now they have been difficult to design at scale.

“Our paper marks a step change in how GPCR medicines can be discovered,” said Christoffer Norn, PhD, CEO and Co-founder of Skape Bio, as well as corresponding author and co-lead on the Nature study. “It shows that we can custom-design protein modulators with defined function and then test them directly on full-length receptors in living human cells, where GPCRs actually signal. For Skape Bio, this technology creates a path toward a new generation of precision protein therapeutics for clinically important GPCR targets where existing drug modalities fall short.”

Skape Bio was founded in 2025 as a spinout of the BioInnovation Institute and the University of Washington’s Institute for Protein Design. The company is building a platform for commercial use that combines AI-enabled protein design with high-throughput screening in living human cells to develop functional miniprotein agonists and antagonists across GPCR targets. Skape Bio is advancing an internal pipeline and partnering with pharmaceutical companies to apply the platform across disease areas.

About Skape Bio
Skape Bio is a biotechnology company developing protein-based medicines for GPCRs, the largest class of drug targets. The company’s platform combines AI-enabled protein design with high-throughput screening in living human cells to generate functional miniprotein agonists and antagonists against clinically important GPCR targets. Spun out of David Baker’s lab, Skape Bio is advancing its own therapeutic pipeline and partnering with pharmaceutical companies to expand the reach of protein-based GPCR drug discovery. The company is currently expanding its team in Copenhagen. To learn more and see open positions, visit skape.bio.