This article was originally published on Feb. 23.
By Ben Butkus
Swift Biosciences, a year-old startup developing molecular biology reagents for research and diagnostics, emerged from stealth mode this week by publicly presenting the first research results for its core technology, a new kind of highly sensitive qPCR primer designed for mutation and low copy number detection.
The company aims to commercialize its first product, likely research-use-only qPCR kits for cancer mutation detection, later this year; and follow those with offerings for the diagnostics and next-generation sequencing space, CEO David Olson told PCR Insider this week.
In the meantime, Swift is seeking to partner with academic institutions and companies to explore additional applications and commercialization routes for its primer technology, Olson said.
Swift, based in Ann Arbor, Mich., first made its presence known in August when it announced it had recently completed a $3 million Series A financing round led by venture firm DFJ Mercury.
At the time, the company said that the new funds would help it accelerate product development and testing for technology that it generically described as "molecular biology reagents for research and diagnostic applications" that would provide customers with "powerful new ways to examine disease-related genes."
Today, the company let the cat fully out of the bag by unveiling its flagship technology, dubbed myT Primers for qPCR assays, in a pair of poster presentations at Cambridge Healthtech Institute's Molecular Medicine Tri-Conference in San Francisco.
As described in one of the posters, Swift scientists developed myT qPCR assays for the seven most frequent KRAS mutations (codons 12 and 13) and the two most frequent BRAF mutations (V600E/K), and evaluated their sensitivity and specificity in both model and clinical samples from colorectal cancer and melanoma patients.
In model tube-based assays, the myT Primer assays were able to detect a single copy of mutant template molecule with a high degree of specificity in that they amplified none of the approximately 14,000 wild-type copies of genomic DNA over 55 cycles.
According to the company, these results were "several orders of magnitude" higher than those achieved using a "leading commercially available KRAS qPCR mutation test kit." Although Swift did not disclose the manufacturer of that kit, it is likely Qiagen's DxS business, which offers such an industry-leading product called TheraScreen K-RAS.
In addition, Swift demonstrated how its assays were effective in clinical samples, achieving single-copy sensitivity for KRAS assays on formalin-fixed paraffin-embedded specimens from Stage III colorectal tumors; and for BRAF assays on FFPE melanoma specimens.
In a second poster, Swift demonstrated proof of concept for using myT primer assays to detect mutations in both circulating tumor cells and cell-free serum or plasma DNA. More specifically, company researchers added limiting dilutions of cultured cancer cells harboring KRAS mutations to whole human blood and subjected the sample to allele-specific myT Primer assays.
Again they were able to detect single copies of mutant alleles in a background of 14,000 wild-type copies; and subsequent plasmid-mixing experiments suggested that the absolute limit for myT Primer analytical selectivity may be as low as one in 100 million.
Swift's Olson told PCR Insider this week that the myT Primers owe their high degree of sensitivity and specificity to a unique physical primer configuration that allows them to function only in a very narrow thermodynamic window.
"If you're in the right thermodynamic window, they work very well as primers," Olson said. "If you're off on thermodynamics, then they don't work very well at all — and that can happen if there is a single base pair substitution in your template, where they would [normally] work at that temperature, but now the [melting temperature] alignment is not quite right."
The upshot is that myT Primers are exceptionally good at "detecting exactly the template you're going after, and they are very finicky about making sure that they only prime that template," Olson added. "So the obvious initial application for that is looking for single-base-pair substitutions, and finding low copy number targets in a sea of high copy number wild type."
Researchers are working on several techniques to achieve a similar result, and perhaps one of the hottest of these new methods is digital PCR, in which a sample is partitioned into much smaller reaction volumes in order to amplify and quantify increasingly smaller amounts of genetic material — down to single transcripts or nucleic acids from single cells.
"Digital PCR goes about it in a different way," Olson said. However, as with many other technologies being developed for low copy number detection, digital PCR "attempts to maximize the signal while minimizing the background," Olson said. "That's difficult to do because any of the Taq polymerases, when given nothing to do, will find something to do with themselves. So priming has to be very specific in order to get the low copy detection in the presence of a lot of wild type."
Olson described the myT Primer assays as "more of a competitive priming situation."
The myT Primer assays can run on any existing real-time PCR platform in a single tube, according to the company. The assays should also allow a high degree of multiplexing within a single tube.
Having demonstrated proof of principle for its technology, Swift has now turned its attention to potential commercialization routes, of which there are several possibilities, Olson said.
"One is bringing these kits out for research use only," he said. "We may be doing direct sales, or we may be doing that through partnerships or distributorships. The second thing, of course, is to get these into the clinic as a diagnostic, and that … we will almost certainly be doing through a partnership. But I would expect the RUO kits to be available later this year."
The company is also seeking to partner with academic institutions and corporations to flesh out additional applications for the myT Primers. Olson said that the company recently initiated its first academic collaboration, and although he couldn't disclose the partner due to the early stage of the partnership, he said that the project will involve additional clinical validation of Swift's technology on a much larger scale.
Further down the road, Swift will be developing and introducing products incorporating both the myT Primer technology, as well as some other proprietary technologies, for next-gen sequencing applications.
"The unique characteristics of those primers lend themselves well to novel ways of creating next-gen sequencing libraries … very quickly and easily, and that have some other positive features to them," Olson said. "We also have some technology that constitutes both materials and protocols that should … basically supercharge the [NGS] capability of existing instruments — better reads, longer reads, that sort of stuff."
Swift said that it estimates the addressable market for its lead products exceeds $1.4 billion, and is projected to grow at a rate of 15 to 25 percent annually.
Swift currently has one patent pending on the myT Primer technology; and has filed additional patents for NGS and some other applications, Olson said. "And we'll have additional patents on the primers as we go along," he added.
The company currently has six full-time employees. It is not seeking additional financing at the moment, but may do so at the end of the year as it ramps up commercialization of its first products, Olson said.
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