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Biofidelity’s $12m will help it transform cancer diagnostics

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The Cambridge start-up Biofidelity is developing simple but astonishingly sensitive cancer diagnostic tests that can be carried out easily in labs across the world. We found out more from CEO Dr Barnaby Balmforth.

Biofidelity is creating cancer diagnostic tests that could be performed in labs worldwide. Picture: Keith Heppell
Biofidelity is creating cancer diagnostic tests that could be performed in labs worldwide. Picture: Keith Heppell

Understanding the genetic changes caused by cancer is vital to delivering targeted therapies for patients.

Much is made, and with good reason, of how DNA sequencing is revolutionising treatment – and heralding a new era of ‘precision medicine’.

But here is a sobering thought from Cambridge start-up company Biofidelity: it says about 95 per cent of cancer patients are excluded from next generation sequencing due to its high cost, complexity and slow turnaround times.

Instead, most patients are assessed with something much less sophisticated.

But that could soon change with Biofidelity’s exciting new technology, which has just attracted $12m in a Series A funding round.

Not bad for a company that was only formed in 2019.

Dr Barnaby Balmforth, chief executive officer and co-founder, says its chemistry-based assays will provide oncologists with a simple, but highly accurate report on an individual patient’s cancer along with details of what drugs can be used.

The company, based in the Broers Building on JJ Thomson Avenue, is starting with lung cancer – and intends to roll out a portfolio of diagnostic tests for other cancers.

“There are about two million new lung cancer cases diagnosed each year,” says Dr Balmforth. “International organisations issue guidelines for how these patients should be tested and treated.

“Every patient should have a test to look for what genetic changes are in their genome and they can be used to target the right therapy. There are a large number of different cancer treatments that can be used in lung cancer. Getting the right one to the right patient depends on that diagnosis.

“There are broadly two approaches for how you do that. One would be a very simple molecular test which can be run in labs around the world, but gives you a small amount of detail and is not very simple.”

Known as PCR, or polymerase chain reaction, this technique is widely used in laboratories around the world, including for Covid-19 testing. It is used to amplify small samples of genetic code, using an enzyme and cycles of heating and cooling, so that it can be detected and analysed.

Barnaby Balmforth, CEO of Biofidelity
Barnaby Balmforth, CEO of Biofidelity

“PCR-based diagnostics typically look at one gene but if you want to assess what the best treatment is for a cancer patient you need to look at least 10 or 12 genes, and ideally more. You can’t do that with PCR,” explains Dr Balmforth.

“What is seen as the future solution is DNA sequencing. There, you can look at a huge amount of information. But despite the fact that DNA sequencing has been around for a while, it’s still horribly complicated and expensive and the results can be really difficult to interpret.

“Some oncologists treating these patients really don’t like sequencing. They’ll take a sample from their patient. They’ll send it away to a centralised laboratory and a few weeks later they’ll receive a report back, which they may not understand very well.

“It can be used to guide treatment, but it’s expensive, slow and only run by a few labs in the world.

“That is the problem we are trying to address. We are trying to get all of the actionable information that could be used to make a decision for a patient – much more than you could get from a PCR test – but with the simplicity of a PCR test, so that virtually any lab in the world could adopt it.

“We want to do it in a way that will give really simple information to a clinician, really quickly and at a lower cost.”

Biofidelity’s solution, then, aims to offer the best of both worlds.

“It’s chemistry-based – so not DNA sequencing,” says Dr Balmforth. “It is not PCR, but it runs on the same instrumentation as PCR, which is great for us, because it means all the labs have the instruments needed to run it. And they’ve just bought a load more of them, because it is also used for Covid-19 testing as well. So there’s a huge existing network of instrumentation that can be used for our assays.

“As it is molecular-based, it is more similar to PCR than DNA sequencing.

“It’s a clever combination of enzymes and bits of DNA that we have used to develop this new piece of molecular biology.”

For each mutation that Biofidelity wants to look at, it designs a specific DNA probe to target it.

Biofidelity is creating cancer diagnostic tests that could be performed in labs worldwide. Picture: Keith Heppell
Biofidelity is creating cancer diagnostic tests that could be performed in labs worldwide. Picture: Keith Heppell

“Then we measure a fluorescent read-out, which tells us whether that mutation is present,” he says. “In that way, it is similar to PCR but PCR is limited because in general each target you look for with it requires slightly different conditions in the assay itself.

“For us, every target we look for uses the same conditions, which means you can look for a very large number of targets at the same time.”

The data that is read out from the test will look familiar to anyone who uses PCR techniques, which should aid adoption.

But what of its sensitivity? Biofidelity says it can detect one mutated DNA molecule in a background of billions of healthy molecules. This is 50 times what can be achieved with FDA-approved PCR-based diagnostics.

And it matches the sensitivity gained from next generation sequencing, which requires error-correction technology. And it simplifies the workflow from more than 100 steps to four.

“We worked last year with Agilent, one of the investors in the company, to test the technical capabilities of the technology. In that work, we looked at both plasma samples and real lung tissue samples and showed that we could detect as little as a single molecule of mutated DNA, even where there is a lot of healthy DNA floating around in the background,” says Dr Balmforth.

“The great thing for us was that the performance was completely consistent between tissue and plasma. That sounds like a minor thing but for molecular testing, that is typically where things fall apart. When you are working with tissue, you normally get a lot of carry-over from the tissue sample that interferes with the assay. We don’t see that.”

It means either a blood test, which could reveal circulating tumour DNA, or a tissue sample could be used to analyse a patient’s cancer.

“We see that as one of the real advantages of it. Because it is simple and relatively low cost, you could do both tissue and blood at the same time, with the same test, if you wanted to, which gives you a really good insight into the patient.

“The tissue gives you information about the primary tumour and what is going on there, while the blood can tell you about metastases and whether there are secondary mutations.”

In order to carry out the correct test, Biofidelity will need to know what mutations to look for – information that is compiled and updated by cancer organisations.

“In lung cancer, there are more than 10 FDA-approved drugs, which each target a different molecular pathway,” he notes.

“We can test the DNA from the tumour and detect which of those molecular pathways is the one to target for a patient, so it is enabling precision medicine, in the same way DNA sequencing is trying to do, but our intention is to make it much more broadly available.

“It is deeply disappointing that DNA sequencing is really only available to top-tier insurers in the US and has not gone much beyond that.

“There is more coming online increasingly, but it won’t be that every patient has it and it won’t be truly sensitive enough to do blood testing.”

Dr Balmforth stresses, however, that sequencing will always have an important role to play.

The NHS is currently rolling out a world-leading Genomic Medicine Service , through which it aims to integrate genomics into routine healthcare.

It builds on the work of the 100,000 Genomes Project, which sequenced whole human genomes to give us a library of information that greatly enhanced our understanding of genetic variants.

Granta Park-based Illumina’s technology – used in 80 per cent of genome sequencing – will be vital, as will the software of Wellcome Genome Campus-based Congenica , which accelerates the interpretation of complex genomic data for NHS clinicians.

The NHS aims to aid the diagnosis of rare diseases for patients, match patients to the most appropriate treatments and improve cancer survival rates through the Genomic Medicine Service.

Dr Balmforth believes Biofidelity will provide another very powerful weapon for clinicians.

Biofidelity is creating cancer diagnostic tests that could be performed in labs worldwide. Picture: Keith Heppell
Biofidelity is creating cancer diagnostic tests that could be performed in labs worldwide. Picture: Keith Heppell

“There will be some cancers where you have to do sequencing, but there are a number of key cancers where you don’t need to, and we’ve been resorting to sequencing because there isn’t an alternative,” he suggests.

“Our initial focus is on non-small cell lung cancer because there are really good, clear guideline recommendations on what you should test for, but they are poorly adopted. The clinical benefits are really well-established, so that is an obvious first target for us.

“Ultimately, what we see is a pipeline of assays that we develop and launch which target different cancers. As the testing guidelines evolve, it becomes more apparent which cancers can be better targeted through this kind of testing.

“Colorectal cancer is a good example. There are well-established markers that should be tested for in colorectal cancer, but there are similar problems with testing there.”

Its funding round was led by BlueYard Capital and backed by investors including Longwall Ventures and Agilent Technologies, a global leader in life sciences and diagnostics.

“The money we’ve raised is about transitioning from a technology development phase into a product development phase. It’s about building the leadership team, the commercial team and the technical team so that we can turn this into a product.

“Product for us is not an instrument. It is reagents and technology. We don’t need to spend tens of millions building a new instrument. We are developing and then manufacturing reagents that can be supplied to labs around the world,” says Dr Balmforth.

“We are building our first assays now. We expect to have those ready for internal clinical validation towards the end of this year and will look to launch our first assays next year.”

It represents swift progress for the company, which was co-founded by Dr Balmforth with Cameron Frayling, who worked together at single molecule DNA sequencing technology company Base4 on the West Cambridge site.

They see the company sitting neatly between those companies aiming to improve the sensitivity of PCR and those focused on sequencing technologies, like Granta Park-based liquid biopsy pioneer Inivata.

It aims to provide its products through direct sale, partnering and collaboration.

DNA sequencing has many great applications - but remains complex
DNA sequencing has many great applications - but remains complex

“It won’t work in every cancer. In some cancers, patients have random mutations and you need to sequence to see where these are, but for cancers where there are known mutations that can be targeted by therapies, this is ideal.

“You could look at a whole range of cancers, like colorectal, melanoma, head and neck cancer, where there are known molecular pathways that are targeted by drugs,” says Dr Balmforth.

The company will expand its team – appointing a chief commercial officer and chief medical officer – as it embarks on its next phase.

Central to the team’s product development thinking will be ensuring the report that is output from the assay is clear.

“I’ve been told stories of oncologists getting 20-page reports from sequencing companies and throwing away the last 19 pages because the useful information is on page one, although it still may not be easy to understand,” says Dr Balmforth.

“For us, it is key that what we present is a report that is straightforward for an oncologist to understand, which will be about grouping the mutations by the molecular pathway that can be targeted by a treatment and indicating to the clinician what treatment would be best for that patient.

“It sounds obvious, but it is not what is happening right now.

“The drugs will be guided by the testing guidelines issued by organisations.

“Every three to six months there are new guidelines, but they also say what is upcoming in the next couple of years, as it is known what drugs are in development, so we’ll ensure what we’re developing covers not just what is recommended now, but what is coming in future.”

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