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Bradford’s Cancer Discoveries Lead To Spin-out Company Success

The discovery by University of Bradford researchers that enzymes found in tumours can be used to selectively target anticancer drugs has led to the formation of a successful cancer therapeutics company.

Incanthera PLC discovers and develops anti-cancer drug candidates, and helps them along the road to market by finding suitable investors at the right time. Listed on the UK-based growth company stock exchange, AQUIS, the company now has five full-time staff and an independent pipeline of products.

Incanthera’s story began with research at the University of Bradford’s Institute of Cancer TherapeuticsProfessor Robert Falconer and Professor Paul Loadman had been working for many years on anti-cancer therapies that target the blood vessels found in tumours. These included colchicine, a traditional remedy for gout, which also has strong anti-cancer properties. But because colchicine acted indiscriminately and was toxic in the high doses needed for use as a cancer therapy, it had been ruled out for use in human patients.

Professor of Medicinal Chemistry

Professor Rob Falconer

By experimenting with peptide sequences linked to the drug, Professors Falconer and Loadman came up with a version of colchicine that could only be activated by a specific protein known as a metalloproteinase, or MMP – found in cancer tumours. As the MMP recognises and metabolises the peptide sequence, the active drug is released in exactly the right location – that is, the tumour itself.

After evaluating a number of different molecules, we found the peptide sequence that worked best. By trialling it first in tissues in the laboratory, then in animals, we could confirm not only that it worked in prostate, breast, lung and colon cancers, triggering the anticancer agent at the desired tumour site, but that we saw limited drug release in other tissues, which meant that it was much safer and didn’t cause significant side-effects.

Professor Rob Falconer, chair in Medicinal Chemistry at the University

Following this initial research, funded by Cancer Research UK and Yorkshire Cancer Research, the team developed the compound further, showing that it worked even better in combination with a standard chemotherapy agent, doxorubicin. ICT2588 was subsequently patented by the University.

Meanwhile, funding from Prostate Cancer UK allowed the researchers to explore using the peptide technology with another drug, paclitaxel, targeted to prostate cancer. The team developed a molecule that could selectively target prostate cancer tumours while sparing other tissue. In animal models, this new molecule, called ICT3205, produced a ten-fold increase in concentrations of the active drug in the tumour - and a ten-fold reduction in the surrounding tissues. This development also proved conclusively that using MMPs to deliver treatments could work with other molecules and cancers.

Working with radiology and imaging experts at Stanford University in the USA, Bradford’s researchers also developed another form of ICT2588 that could be attached to an iron oxide nanoparticle. Iron oxide is a contrast agent for MRI scans, and the new molecule enables clinicians to use MRI scans to trace where the drug is going within the body, and see the concentrations accumulating in the tumour. In addition, this molecule – known as ICT-CLIO - was able to penetrate and act on the brain tumour glioblastoma more effectively than the standard treatment temozolomide.

The Bradford research had shown that ICT2588 and its offshoots clearly had drug development potential, and in 2010 the University helped to establish a spin-out company called Incanthera, initially to commercialise the molecule. The company acquired the patent for ICT2588, and secured £375,000 development funding from the private equity firm SPARK Impact. Incanthera’s initial aim was to find a partner company that would take ICT2588 to a clinical trial. The company has since raised over £4 million in private venture capital funding to progress the treatment through its preclinical evaluation.

In July 2017, in Incanthera’s first commercial deal, Ellipses Pharma acquired the rights to ICT2588 for £4.9 million. Ellipses are now taking the treatment to clinical trials, which are expected to start in 2022.

Incanthera has also acquired the rights to other therapies that target keratosis and melanoma, as well as lung, breast, ovarian, prostate, brain, liver and bladder cancers. Professor Falconer says: “Incanthera has taken on a life of its own with an independent pipeline of products. Although initially created to commercialise our research, it also set out to acquire new technologies that are not yet clinic-ready, and develop them enough to find investors to take them on further. It is now doing that very successfully.”