This article was edited to clarify that Aspyre Lung for liquid biopsy has already been launched.
NEW YORK – Biofidelity is hoping to improve minimal residual disease (MRD) testing and cancer patient monitoring with the rollout of its Enspyre sample enrichment platform.
Contrasting with but also complementing the company's PCR-based Aspyre technology and Aspyre Lung assay, Enspyre offers to reduce the cost of running next-generation sequencing-based mutation detection assays by reducing the amount of noise that stems from uninformative sequences.
Barnaby Balmforth, cofounder and CEO of Biofidelity, said that the company is marketing Enspyre in an "Intel Inside" fashion, such that it serves as a core sequencing prep platform for other companies' products.
Balmforth said the company sees itself as developing technology and supporting partners who are developing new oncology genomics products but are limited by a significant signal-to-noise obstacle in which massive quantities of normal DNA overwhelm the search for extremely low-frequency mutations, Balmforth said.
Biofidelity aims to increase this signal-to-noise ratio with Enspyre, which is essentially a modification to standard hybridization capture that specifically captures mutated molecules within the regions of interest using "bait probes," then removes the vast majority of the wild-type DNA with a "washing" step. Biofidelity says this results in an approximately 100-fold improvement in the enrichment of mutated molecules, reducing sequencing depth requirements and helping to streamline the associated data handling and bioinformatics overheads.
Balmforth said that the platform is also capable of being scaled up to mutation panels that number in the tens of thousands.
The Cambridge, UK-based company mainly sees applications for Enspyre in oncology minimal residual disease (MRD) testing, early cancer detection, and patient monitoring, and Balmforth said that the company is currently in discussion with "a number" of undisclosed potential partners for deploying the new technology.
Although Biofidelity primarily focuses on oncology, Balmforth noted that Enspyre can also be applied to many other settings, including agrigenomics and infectious disease.
"In all of those areas, there are applications where this technology could be really impactful," he said. "Those are not our specialties as a company, [which is] one of the reasons why we see this really as partnership driven."
Balmforth said that Enspyre also complements the company's PCR-based Aspyre technology and Aspyre Lung cancer mutation detection assay, and that both can easily be implemented together in many workflows.
"We see Enspyre wrapping around Aspyre and enabling [a] pipeline of products throughout oncology to be built on an underlying molecular biology platform," Balmforth said.
The Aspyre technology, which can be used on existing PCR instruments, also uses probes that hybridize to normal and mutant DNA but are mismatched to the normal DNA, such that a DNA polymerase can only digest the perfectly matched mutant probes, according to the company's website. The digested probes are then selectively circularized by ligation and, in turn, selectively amplified and detected.
The company uses this technology in Aspyre Lung, a lab-developed, research-use-only test that detects 114 mutations in 11 genes, including DNA and RNA biomarkers, relevant to non-small cell lung carcinoma from tissue samples. Late last year, the company launched a version of the assay that also analyzes liquid biopsy samples in cases where tissue specimens are unavailable.
Biofidelity has been offering Aspyre Lung in a series of partnerships over the past year. Early last year, for example, the company signed a deal with Fidelis to supply the assay to active US military and Veterans Affairs medical institutions, and last week it entered into another deal with CellCarta to validate Aspyre Lung in clinical trials taking place in the US and in Europe.
Additionally, Biofidelity also recently published two peer-reviewed articles evaluating Aspyre Lung and has more in the works.
"A big focus for us throughout 2025 will be clinical data generation with Aspyre to support [US] regulatory submissions," Balmforth said.
One study, published in Frontiers in Oncology, tested the limit of detection, specificity, analytical accuracy, and analytical precision of Aspyre Lung using FFPE lung tissue samples from patients with non-small cell lung carcinoma, variant-negative FFPE tissue from healthy donors, and FFPE-based contrived samples with controllable variant allele fractions. The assay showed 100 percent sensitivity and specificity even at low tumor content, with a limit of detection of under 3 percent variant allele fraction for DNA variants and less than 100 copies for RNA fusions.
The second study, published in Translational Lung Cancer Research, demonstrated the ease and reliability with which the Aspyre Lung Reagents can be set up and run in different laboratories. That study evaluated the implementation and use of the kit at Biofidelity's CLIA-certified and CAP-accredited lab in North Carolina, as well as at the Hospital of the University of Pennsylvania and the Precision Medicine Laboratory at the Medical College of Wisconsin. A comparison of results derived from 77 patient samples and run at all three sites yielded a positive percent agreement of 100 percent and negative percent agreement of 99.99 percent.
Balmforth said that the company is currently conducting several other studies that it expects to publish in the near future. The firm is also actively recruiting for a study assessing the use of Aspyre Lung in early-stage lung cancer patients.
Additionally, Balmforth said that the company is conducting an internal study to evaluate Aspyre Lung's capabilities in the context of very low-input samples.
All assays, Balmforth said, have minimum nucleic acid requirements and in cases where a sample is very limited, as often happens in real-world scenarios, the sensitivity of a given test can fall roughly by a factor of 10.
"We've already generated some data showing that from tissue, we can reduce our input requirements really dramatically and still retain high sensitivity, and we're running some studies now on liquid biopsies," he said. The data generated so far, he added, has made the company "really confident."
While the company continues to work with other laboratories, who are considering the assay for in-house research use, Balmforth said that the ultimate goal is to win regulatory approval for Aspyre Lung as a clinical product.
Biofidelity envisions that Aspyre Lung and Enspyre together will enable the development of solutions across the cancer patient journey.
"Aspyre is perfect for rapid treatment decisions and clinical trial enrollment," he said, "whereas Enspyre is ideally situated for MRD and patient monitoring, with potential applications in early cancer detection."