Bicycles address therapeutic needs unreachable with any other existing modality.
An entirely new class of therapies
Based on groundbreaking work conceived in the laboratory of Sir Greg Winter and Professor Christian Heinis, we are pioneering the development of bicyclic peptides, or Bicycles® — a new class of versatile, chemically synthesised medicines. Bicycles address therapeutic needs unreachable with any other existing modality. Their small size and exquisite tumour targeting delivers rapid tumour penetration and retention while clearance rates and routes can be tuned to minimise exposure of healthy tissue and toxicities.
Key properties of Bicycles
Chemically synthesised with plasticity for multimerization and conjugation
Low molecular weight (1.5-2kDa), delivering attractive PK and profound tissue penetration
Large binding footprint allowing targeting of protein-protein interactions
Renal elimination minimising cell interactions in liver and gut
Unique advantage for drug combinations
Classified as small molecules by regulatory agencies
Easily scalable with well-established routes of manufacture
A flexible, modular platform
Bicycles are highly flexible, allowing rapid molecular assembly into more complex molecules.
Bicycles can be used to generate more complex molecules
Bicycles can be used to modulate single targets as stand-alone therapeutics
Bicycles can be linked as tandem or multimeric Bicycles to deliver combination poly-pharmacology
Bicycle Toxin Conjugates
Our Bicycle Toxin Conjugates are tripartite molecules using a Bicycle to recognise and bind to a tumour-expressed target, a tumour microenvironment cleavable linker and a cytotoxin payload. The linker and coupling chemistry hold the payload inert until the conjugate is localised in the tumour microenvironment. This targeted approach rapidly delivers payloads into solid tumours, with extensive tissue penetration, a short duration of systemic exposure and liver-sparing rapid renal elimination. These properties limit the body’s exposure to toxin to control any damage to normal tissue.
Bicycles can be chemically coupled to deliver other molecular cargoes with high target specificity
A unique screening platform
Our unique optimised platform combines biology with chemistry – we utilise synthetic biology to display an unimaginable diversity (quadrillions) of linear peptides on the surface of engineered bacteriophages and chemistry to transform them into Bicycles. We can rapidly select those that bind to a chosen biological target and use evolution-driven, informed selection to drive hit to lead and rapidly derive optimum molecules.
Our screening platform can be deployed to screen either soluble proteins or cell-based targets. The process is resource efficient and rapid and, uniquely, uses an integral on-phage binding assay which informs structure activity relationships. We can incorporate a diverse range of small molecule scaffolds into Bicycles to increase diversity and confer differentiated physicochemical and structural properties.
We have demonstrated unprecedented success selectively drugging diverse target classes, including cytokines, chemokines, enzymes, proteases and a diverse collection of cell surface receptors (GPCRs, extracellular tethered enzymes and receptor tyrosine kinases).
A breadth of therapeutic opportunities
We are rapidly advancing our robust pipeline of Bicycles for oncology, while pursuing collaborative partnerships with other companies in additional disease areas. This strategy enhances our ability to bring this important class of medicines to patients with debilitating diseases.