Discover and translate – a mantra to work by

You are the co-founder and scientific lead of ManTRa Diagnostics, a spinout company made possible by the work done in your lab. Could you briefly walk us through ManTRa diagnostics and how it came about?

“It can be hard to juggle academic work while trying to spin out a company. There have certainly been times when I’ve questioned the decision to take on the extra work, but I’m so glad I did!” Professor Catharine West. 

Much of the work in my lab has focused on developing gene signatures that could be used to assess the hypoxia status of solid tumours.

We know tumours that are the most hypoxic have a poor prognosis – irrespective of the type of treatment. We also know that giving hypoxia-targeted treatments can improve survival outcomes. For years, people have been exploring different approaches for measuring tumour hypoxia, and more recently there’s been a specific focus on deriving gene signatures because this is one of the ways we could create a clinically useful test for patient stratification.

Hypoxia gene signatures have been developed for several tumour sites and validated in multiple cohorts. We showed that a bladder cancer signature we developed can predict patient benefit from hypoxia-modifying radiotherapy. Patients with hypoxic tumour had a 30% increased chance of being alive three years after starting treatment if they had this treatment. Patients with no hypoxia in their tumours derived no benefit.

After validating the performance of the signature, our next step was to try and use it to determine a patient’s treatment. It was difficult to see how to get it into the clinic without commercialising it first, and so this where ManTRa Diagnostics started.

If a test result is going to be used to determine choice of treatment, it needs to be performed in an ISO accredited environment, and there is in turn a whole raft of assay validation that is required for ISO accreditation. That kind of work isn’t always attractive for research funders, so we spun out the company to try and get the resources so that our signatures could actually be used for cancer patients.

What technological advances have enabled ManTRa DX?

Discovering a biomarker is, as these things go, relatively easy. However, trying to progress it to the stage where it is useful requires assay development and extensive validation – not very ‘sexy’ types of research. However, advances over the past 20 years have been amazing, a perfect example is of course our ability to measure the expression of whole genomes. Also, access to datasets like The Cancer Genome Atlas have made a big difference – it means you can validate signatures in multiple cohorts.

There have also been continuous improvements in the technology for measuring the RNA expression of a group of genes. We started using a PCR-based test, but now we’re in the process of moving to NGS technology, which is likely to be the future for clinical testing of gene signatures. One of the challenges has been trying to keep up with developments in technology and picking one that is likely become widely available in clinical testing laboratories – both NHS and private providers.

What challenges lie ahead for ManTRa DX?

Our main challenge is to obtain funding and investment. It’s been very time consuming developing a business case and having all the meetings that come along with forming a start-up. If we don’t get investment, ManTRa Diagnostics will not go ahead.

There are also a number of self-doubts that creep in. Can clinicians be persuaded to use the test? Do we need a companion therapeutic? Do we have the data to persuade the NIHR and FDA that the tests are useful? Are prospective clinical trials needed to demonstrate the benefit of the signatures? Will lack of intellectual property prevent investment?

There are clearly a lot of challenges… so what has it been like combining an academic career with commercial translation?

The truth is that it can be hard to juggle academic work while trying to spin out a company – there is rarely protected time in academia for trying to commercialise.

Generally speaking, academia requires publications whereas commercialisation requires protection. There have certainly been times when I’ve questioned the decision to take on the extra work, but I’m so glad I did! The past three years have fascinating, and commercial translation is the best route for trying to get the signatures into clinical use for patient benefit.

What would be your best advice for a researcher who might want to start their own spinout company?

As a researcher it can sometimes feel conflicting to try and push commercialisation when patient benefit is the goal rather than monetary gains. However, if you look at the scientific literature, it is littered with biomarker discoveries yet very few of them are translated into the clinic. There needs to be a smarter way of taking the journey that starts with consideration of commercial opportunities.

Think before starting the research – ask yourself what might be needed for commercialisation in terms of both IP and generating the right sort of data.

Over the years I’ve increasingly out-sourced lab work – DNA extraction, microarray, RNAseq etc. It is more cost effective than paying for technical staff and equipment service charges. Find companies that have the facilities for ISO accredited working and standardised operating procedures. It would be worth finding a company that provides tests for clinical use and developing a relationship with them from the start.

This is an exciting time for cancer diagnostics – how do you see the field evolving over the next decade?

Future cancer treatments must involve increasing personalisation based on an individual patient’s tumour biology. Each year brings new innovations for treating cancer, but new anti-cancer agents often fail in clinical trials in part due to testing on unselected patients.

Only some patients benefit from the different types of chemotherapy, small molecule inhibitors, engineered agents and from treatments targeting hypoxia. This of course means there will be an ever-increasing demand for prognostic and predictive gene signatures. And as they increase in number, it will be possible to take biopsies and measure several signatures in a single test. My focus has been on RNA, but DNA mutations will also be assessed.

Questions prepared by Arthur Combeaud