LONDON – Biofidelity Ltd. has raised US$12 million in a series A, enabling it to start commercialization of a novel, low-cost, chemistry-based diagnostic for detecting all actionable lung cancer mutations.

The Cambridge, U.K.-based company claims the test can detect a single molecule of mutated DNA against the background of billions of healthy molecules in a patient sample, without the need for DNA sequencing. The chemistry can be multiplexed to enable simultaneous detection of large panels of DNA mutations at extremely low frequencies, making it suitable for use for a broad range of cancers.

In a study carried out in collaboration with Santa Clara, Calif.-based Agilent Technologies Inc., the lung cancer assay developed by Biofidelity showed a 50 times improvement in sensitivity compared to current FDA-approved polymerase chain reaction (PCR) based diagnostics, matching the performance of liquid biopsies that use next-generation DNA sequencing.

The assay runs on standard PCR instruments and installed laboratory infrastructure, opening the way to widespread use of high sensitivity, noninvasive genetic testing, said Barnaby Balmforth, CEO and co-founder of Biofidelity.

“A key goal for us as a company is to try and enable much broader access to high precision diagnostic tests. There is a fundamental problem at the moment that these are not accessible. Liquid biopsies offer amazing accuracy, but the complexity and costs and the need to centralize in a small number of labs, limits access,” Balmforth told BioWorld.

Details of exactly how the chemistry works are confidential for now, but Balmforth said, “We are looking for changes in DNA, but not through sequencing. It is a chemical reaction that is as simple as PCR.” The method will be disclosed “in the coming months” in a report on the Agilent lung cancer study.

According to Biofidelity, 95% of cancer patients are excluded from the next-generation sequencing tests currently available for detecting mutations that are addressed by targeted cancer drugs.

For those patients that do get access, turnaround times can be up to four weeks.

Biofidelity says its method allows for “dramatic simplification” of workflows. While there are more than 100 steps in next-generation DNA sequencing assays, its test can pick up mutations in multiple genes in just four steps.

Analysis of results is also far simpler, and based on these improvements, physicians can get a clear and simple result that provides the evidence needed to prescribe a targeted drug in less than three hours.

Balmforth said these advances in reducing costs and shortening turnaround times open up the possibility of carrying out repeat testing to monitor for the development of resistance, enabling patients to be switched to alternative therapies. “You can’t test every eight weeks at the moment. In future you would be able to,” he said.

In addition to being able to pick up the very small fraction of tumor DNA present in blood samples, the method is equally effective at detecting mutations in solid tissue biopsies. That is significant because standard of care solid tissue profiling has been found to pick up 26% fewer actionable mutations than through sequencing of circulating tumor DNA.

In the Agilent study there was both 100% sensitivity and 100% specificity in the detection of multiplexed panels of mutations from both tissue and plasma. No false positives were observed across more than 750 assays.

“We are not purely targeted on liquid biopsy. There are some real problems in the accuracy of tissue testing that our technology can address,” said Balmforth.

At the same time, around 20% of cancer patients do not have any detectable circulating tumor DNA, making liquid biopsies unsuitable. “We believe we can address the limitations of both tissue and liquid biopsies,” Balmforth said.

With the closing of the series A, Biofidelity is ready to move from technology development to product development. “We are taking the technology and putting together a pipeline of assays,” said Balmforth.

The assays initially will be launched in the U.S. as laboratory developed tests, enabling data to be generated for FDA approvals as in vitro diagnostics. Earlier this month, Guardant Health Inc.’s tumor mutation diagnostic became the first DNA sequencing/liquid biopsy test to be approved by FDA. That followed its initial introduction as a laboratory developed test, Balmforth noted.

Biofidelity also has had preliminary discussions with some pharma companies about the development of companion diagnostics for specific targeted therapies.

After closing the series A, the aim now is to get the first assay in use in a small number of labs over the next year, leading on to the raising of a second round of financing.

The series A was led by Blueyard Capital, with Longwall Ventures and Agilent also contributing. Biofidelity previously raised £750,000 (US$980,805) in seed money in September 2019, after it was spun out of another diagnostics startup Base4 Innovation Ltd., by Balmforth and co-founder Cameron Frayling.

In October 2019, Biofidelity won a £500,000 grant from the government innovation agency Innovate UK to fund the collaborative study with Agilent through which the technology has been validated.

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