

Platform
A Modular Platform
Bicycles can be identified that deliver multiple different pharmacologies. Not only that, but they can also be combined with other payloads to deliver potentially innovative solutions.
Bicycles can be used to generate more complex molecules, and can be delivered as stand-alone molecules, linked together as bi-specifics, further elaborated into higher order Bicycles, or linked with other small molecules, nucleic acids or biologics to act as a precision-guidance mechanism.
Bicycles can be used to modulate single targets as stand-alone molecules
Bicycles can be linked together as bi-specifics, which simultaneously bind to two different proteins to deliver dual pharmacology.


Bicycles can be further elaborated into higher valency multimeric Bicycles to deliver more complex pharmacology.
Payloaded Bicycles
Bicycles can be linked to other non-Bicycle payloads, such as other small molecules, nucleic acids or biologics. This allows the Bicycle to act as a precision guidance mechanism, where potentially tissue- or tumor-targeting Bicycles binding to selectively expressed targets may be able to deliver the conjugated payload directly to the intended site of cellular action.
A precise guidance system for the delivery of a payload directly into a tumour, with the potential for sparing bystander cells and tissues not involved in the disease.
An example of payloaded Bicycles is our Bicycle toxin conjugates. These contain a Bicycle targeted to a specific tumor antigen, a selectively cleavable linker, which is selectively cleaved by enzymes upregulated within the tumor microenvironment, and a small molecule payload. The linker and coupling chemistry hold the payload inert until the conjugate is in the tumor, whilst the Bicycle guides the precise delivery of the payload into the tumor – the desired aim for this being to spare healthy cells and tissues, while at the same time potentially destroying the tumor.
TfR1 Bicycles
A second example of payloaded Bicycles is our transferrin delivery system. This comprises a Bicycle targeting TfR1 (CD71), a high-capacitance transporter with a normal function in iron transport, coupled to short RNA cargos, either antisense oligonucleotides (ASO) or short-interacting RNAs (siRNA). These will potentially allow the selective delivery of therapeutics into TfR1 expressing tissues, such as skeletal and cardiac muscle as well as into the central nervous system (CNS).