Abstract

Bicycles^® are
peptides constrained via conjugation to a small molecule chemical scaffold and
represent a new therapeutic modality with unique and favourable drug-like
properties. The
proprietary Bicycle phage display platform has been optimised over 10 years and
over 100 screening campaigns to a range of diverse and challenging targets so
that it generates highly selective, highly stable Bicycles, often with sub-nM
affinity. Bicycles can generate enormous chemical diversity, by varying amino
acid content at each position, loop size and loop symmetry or by exchanging the
central chemical scaffold. Currently we have > 100 phage libraries that
sample >10¹⁷ sequence and structurally diverse molecules. Because
of the way Bicycles are selected, by phage display, they self-select to be
amenable to conjugation; either with each other to make complex multimers, or
to other small molecule cargo, without perturbing their binding affinity
to the designated target. Bicycle has a strong pre-clinical pipeline and is
progressing its lead molecule BT1718 (a Bicycle Toxin Conjugate) in a Phase1/2a
trial partnered with CRUK.