ICT01-2588 has been developed by the research group of Prof. Laurence Patterson at Institute Cancer Therapeutics, University of Bradford.
ICT01-2588 is a novel vascular disrupting agent (VDA) and drug delivery platform that comprises a colchicine derivative “warhead” linked to a stable peptide chain by a spacer designed to be cleaved by MMP14, an enzyme over-expressed in many human cancers. In the laboratory, ICT2588 achieves tumor selective delivery of the VDA leading to reduced tumor blood flow and tumor shrinkage without significant toxicity.
ICT2588 is a peptide-conjugate of azademethylcolchicine (aza-d-colch), with the peptide sequence rationalised to be specifically cleaved by membrane-type-1 MMP (MT1-MMP; MMP-14). The Incanthera strategy is not, however, to inhibit the MMPs, as was attempted with agents such as marimastat. Rather, Incanthera are looking to exploit the functional activity of MT1-MMP to hydrolyse a peptide-conjugated agent and release a potent VDA directly into the tumor.
In the preclinical development, ICT01-2588 showed very promising efficacy and PK profile in xenograft models. Administrated in combination with another standard of care drug ICT01-2588 achieved clinical cure in 60% of treated animals. ICT01-2588 is due to begin Phase 1 clinical trial, starting 2018.
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patients survive cancer for ten or more years (CRUK)
Cancer survival in the UK has doubled in the last forty years