NEW YORK – Xgenera, a Southampton, UK-based molecular diagnostics startup, has received two government grants to help develop a microRNA-based test for detecting cancer, including the ability to identify the site of origin, into a viable commercial product.
CEO Andy Shapanis said that Xgenera has received a £2.5 million ($3.3 million) grant from the UK National Institute for Health and Care Research to support development of its Mionco-Dx Test. Xgenera also received a £100,000 grant through Innovate UK's Cancer Therapeutics program, which awarded a total of £12 million in September.
According to Shapanis, Xgenera also last month closed a round of seed financing worth £500,000 and commenced a partnership with YouSeq, a UK technology firm based in nearby Winchester that specializes in the manufacture of next-generation sequencing and quantitative PCR kits. As part of its agreement with YouSeq, the company will also gain access to office and laboratory space, he said.
"They are supporting us in getting the best qPCR assay possible," Shapanis.
With the funds from the government grants and financing, plus the new partnership, the year-old company is progressing with its plans to move its multicancer early detection test to a qPCR platform, so that it can be validated in a new cohort and, ultimately, made available for clinical use. The test, he said, was developed with array data, but qPCR is the optimal platform.
"qPCR is more ubiquitous than microarray," said Shapanis. "It's cheaper, faster, easier."
It also might give the bantamweight firm an advantage against bigger players like Grail. The UK National Health Service is currently assessing Grail's next-generation sequencing-based Galleri test in a three-year prospective trial involving 140,000 people. The trial is set to finish in 2026, at which time the NHS will decide on implementing Galleri throughout the nation's health system.
"qPCR is orders of magnitude cheaper than next-generation sequencing," remarked Shapanis. While it's unclear how much the Galleri test will cost when and if it is made available in the UK, the list price is $949 for the test, which Grail said is able to detect more than 50 forms of cancer at an early stage from a blood sample.
"Nine $50 PCR tests are still cheaper than an NGS test," said Shapanis. "qPCR is also easier to adopt, as everyone knows how to run it, and it doesn't require the bioinformatics downstream."
For Shapanis, transferring Xgenera's marker panel to qPCR will be the latest move in an ongoing story that began with his work as a senior research fellow at the University of Southampton, where he earned a Ph.D. in 2019 in oncology and cancer biology. A self-described computational biologist by trade, he originally looked at crafting a protein-based assay to tackle the problem of diagnosing cancer early in asymptomatic patients and providing information on the site of origin with the same test.
He said the resulting assay worked well but was noisy, which made him turn toward transcriptomics, which has its own pitfalls.
"With proteins, there are hundreds of thousands of them, but each one has different versions," said Shapanis. "There's a lot of noise to get lost in." He noted that at the genomic level, an alternation is not always predictive of disease. This led him to search for an "in-between balance," somewhere between high and low resolution. He found this sweet spot with miRNAs.
Shapanis also amassed a set of array data on some 21,000 individuals and used this cohort to select 50 miRNA markers that he found to be predictive for certain cancers, as well as to provide site of origin information. Currently, Xgenera claims its test can detect at early stage the 12 most common cancers — lung, breast, prostate, pancreatic, colorectal, ovarian, liver, brain, esophageal, bladder, bone and soft tissue sarcoma, and gastric.
Paired with in-house-developed machine learning tools, the miRNA classifier, which also includes five controls for a total set of 55 markers, forms the basis of the Mionco test.
Shapanis initially considered publishing his findings, but was encouraged by Paul Skipp, a professor of proteomics and director of the Centre for Proteomic Research at the University of Southampton, to explore a commercial route. Skipp is also the founder and director of TopMD Precision Medicine, an artificial intelligence company focused on identifying biomarkers for diagnosing disease and informing treatment. He is also now a founder and CSO at Xgenera.
"He's been pivotal in helping me turn this into something," Shapanis said of Skipp.
The company now wants to move the Mionco test to qPCR. This will be accomplished with the £2.5 million grant from the National Institute for Health and Care Research. The project, which commenced this month, is about getting the test into the new format and improving its turnaround time. "We call it optimization of scalability," said Shapanis, adding that Xgenera will focus on reducing cost, increasing throughput, and streamlining adoption during the process.
Xgenera will also validate the test in another 8,000 samples as part of the effort. These samples will be drawn from other studies. "There are many studies with relevant samples out there," he said. "We're going to utilize those so we don't have to do prospective collection," he said.
Samples will include those from presymptomatic and asymptomatic patients, he underscored.
"We're aiming for a screening test, something that can be used in an asymptomatic population, before they even have clinical symptoms," Shapanis noted. "We want to be able to prove, at least in principle, that it can be used in those really early stage patients."
Xgenera will also be looking to refine its marker set in the process, gauging the performance of each miRNA marker. This could lead to a reduction in the number of markers. Shapanis said that all 50 markers aren't necessary to detect tumor sites of origin, but that a "layer of redundancy" has been built into Mionco to improve its performance.
The Innovate UK grant, meantime, will be used to support developing new ways of running miRNA analysis on qPCR going forward. Both grants will also allow Xgenera to hire new personnel. These hires will largely be on the R&D side, Shapanis said, as the company looks to add molecular biologists, bioinformaticians, and technicians.
The price of the test is still to be determined, and while some recent UK news articles cited a price tag of between £120 and £300 for Mionco, Shapanis said such projections are premature.
He declined to price the test. "We're still early in the development process," he noted. "What I can say is that we are trying to make it as affordable as possible to make it as accessible to as many people as possible."
By the end of the NIHCR grant in three years, the company intends to have a "final locked product" in place for which it will seek both UKCA marking and CE-IVD certificates under the EU's In Vitro Diagnostic Regulation, Shapanis said. Xgenera is also considering doing a large-scale prospective clinical trial of its test, similar to what Grail is currently doing with the Galleri test.
The test itself may undergo future updates. Skipp said in an email that "most certainly the plan is to extend the number of cancers, though this will naturally require further work and validation." Xgenera also sees an opportunity to extend its platform to monitoring minimal residual disease in response to therapeutic interventions, he said.