The Global Cyclopeptide Industry

Circle Pharma is developing macrocyclic peptides engineered to achieve cell permeability — enabling them to reach intracellular drug targets that have historically been considered undruggable. Conventional small molecules are too small and non-selective to disrupt most intracellular protein-protein interactions; antibodies are too large to enter cells at all. Macrocyclic peptides of the kind Circle develops occupy a productive middle ground: large enough to engage complex binding surfaces, compact enough to cross cell membranes under the right conditions.

The company is backed by leading biotech investors including The Column Group and Nextech Invest, and has raised $117.5M in total funding. Its oncology focus targets transcription factors and protein-protein interactions that drive cancer growth — a class of targets long considered off-limits to conventional drug modalities. Circle's platform represents the convergence of medicinal chemistry expertise and the structural insights emerging from cyclotide and macrocycle research.

Insamo is an AI-driven cyclic peptide design startup focused on the specific challenge of creating orally available, cell-permeable cyclic peptides. The company raised $12M in seed funding in June 2024. Oral bioavailability has historically been the defining challenge for any peptide therapeutic: most peptides are destroyed by digestive enzymes before reaching the bloodstream, and those that survive often fail to cross intestinal membranes. Cyclotides solved this problem through evolution over millions of years; Insamo's approach is to solve it in months using machine learning.

The company uses deep learning models trained on structural and pharmacokinetic data to navigate the vast chemical space of cyclic peptide sequences, predicting which combinations of amino acids will yield both target binding activity and the passive permeability required for oral absorption. This computational-first approach can dramatically compress the discovery timeline compared to traditional empirical screening, and positions Insamo as a drug discovery partner for pharmaceutical companies seeking cyclic peptide leads against specific targets.

Unnatural Products is a macrocycle technology company that attracted significant industry attention in 2023 when it announced a landmark $220M collaboration with Merck for oncology drug discovery — one of the largest deals ever struck around cyclic peptide technology. The partnership focuses on using Unnatural Products' proprietary cyclic peptide libraries and screening platforms to identify drug candidates against oncology targets that are inaccessible to small molecules. The company also raised a $32M Series A in December 2023, reflecting investor confidence in its platform independent of the Merck relationship.

Unnatural Products' approach centres on building and screening ultra-large libraries of structurally diverse cyclic peptides — a combinatorial strategy that exploits the vast sequence space available when non-natural amino acids and novel cyclization chemistries are incorporated. The Merck collaboration validates the commercial and scientific credibility of the macrocyclic peptide class for major pharma, and signals that the industry now views cyclic peptide drug discovery as a viable mainstream strategy rather than a niche research area.

CyclicTx operates an AI-powered cyclic peptide design platform, using computational approaches to design and optimise cyclic peptide drug candidates for pharmaceutical partners. The company focuses on bridging the gap between computational prediction and wet-lab validation — generating cyclic peptide leads computationally, then rapidly iterating through synthesis and testing cycles to converge on optimised candidates. CyclicTx's platform is designed to be target-agnostic, enabling pharma partners to bring undruggable targets and receive optimised cyclic peptide leads in return, compressing the traditional discovery-to-candidate timeline.

Pepscan is a global leader in peptide cyclization technology, known primarily for its proprietary CLIPS (Chemical Ligation of Peptides onto Scaffolds) platform. CLIPS enables the controlled cyclization of peptides into defined three-dimensional shapes, constraining their conformation and dramatically improving their target selectivity and binding affinity. The technology can also be used to create bicyclic and polycyclic peptide structures — adding further levels of structural complexity that can improve drug-like properties including cell permeability and metabolic stability.

Pepscan targets oncology, infectious diseases, and autoimmune disorders, both through proprietary drug development programmes and as a contract research organisation providing cyclization services and peptide library screening to pharmaceutical clients worldwide. The company's European base and established technology platform make it one of the few organisations with deep cyclization chemistry expertise at commercial scale.

Chugai Pharmabody Research — the drug discovery arm of Chugai Pharmaceutical, itself a majority-owned subsidiary of Roche — runs an active cyclic peptide drug discovery programme. Leveraging Roche's deep oncology pipeline and Chugai's expertise in antibody engineering and structural biology, the programme seeks to develop cyclic peptide drug candidates against intracellular targets that antibodies cannot reach. The involvement of a Roche-group company in cyclic peptide research is a significant signal: it reflects the belief among the world's largest pharmaceutical groups that macrocyclic peptides represent a viable next-generation modality, not a speculative bet.

Chugai's entry into the space also brings the resources and regulatory expertise of a global pharmaceutical company — accelerating the path from discovery to clinical development in ways that are difficult for smaller startups to replicate independently.