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Oxford Spinout to Develop Cancer Therapies that Reprogram Tumours to Die

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Oxford University spinout Argonaut Therapeutics is developing cancer drugs that reprogram cancer cells to undergo the body’s natural process of cell death, shrinking tumours.

The company will focus on treatments for colorectal cancer and lymphoma.

Argonaut has raised seed funding from investment company Oxford Sciences Innovation to develop and test a set of drug candidates, as well as biomarkers that allow physicians to determine which patients are most likely to respond well to the new drugs.

Argonaut founder Professor Nick La Thangue is Chair of Cancer Biology at the University of Oxford. He said: ‘Cancer drugs are relatively ineffective in as many as 70% of patients, in part due to genetic variations between patients. The demand for precision, personalised medicine is increasing. It is a cost-effective way of detecting disease earlier and it allows us to tailor therapies for each patient.

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‘Our approach is to reboot the cancer cell so it undergoes normal cell death, a process called apoptosis. Cancer is a result of lack of cell death, or uninhibited cell division. We plan to stimulate tumour cell death, causing cancerous tumours to shrink.’

Argonaut will develop therapies that t arget a ‘switch’ that directs cells to either grow and divide or to die. This switch – a transcription factor that binds to a cell’s DNA – is controlled by an enzyme called PRMT5. When the transcription factor is methylated by PRMT5, it is in the proliferation mode, and when it is inhibited it activates the ‘cell death mode’.

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Professor La Thangue said: ‘The beauty of this approach is that we can also predict whether tumours are likely to respond, as we can test whether the transcription factor is methylated or not. Our drug candidates target this transcription factor, with the aim of reinstating the body’s natural cell death processes, shrinking tumours naturally rather than causing general cytotoxicity, which is how many current cancer drugs work. We believe the combination of our approach and other new immunotherapies could mean physicians are able to tackle cancer in a different and potentially very powerful way.’

Professor La Thangue’s group has designed a series of pre-clinical candidate compounds, which it will assess to identify lead compounds to take into clinical trials. The company plans to undertake clinical trials at the Churchill Hospital’s clinical trial centre.

Adam Stoten, Head of Technology Transfer (Life Sciences) at the University of Oxford’s technology transfer company, Oxford University Innovation, added: ‘Argonaut is a great example of designing new drugs which, from the earliest stages of development, are coupled with biomarkers able to direct treatment to those patients most likely to respond. Ultimately this has the potential to optimise both patient benefit and value for healthcare payers.’

Argonaut is based at the Oxford Science Park.

Colorectal cancer is the second most common cancer and affects 40,000 new patients in the UK each year. New treatments are in high demand as current treatments offer limited efficacy.

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