BALTIMORE – Drumming up for the debut of its CosMx spatial multiomics imaging platform later this year, NanoString Technologies offered technical sneak peeks this week while showcasing early interest among researchers.
Despite a looming patent infringement lawsuit filed by 10x Genomics and remaining technical details to be refined, NanoString said it is now "actively promoting" CosMx and expects "to accumulate dozens of orders" ahead of the first commercial shipments in the fourth quarter.
In a conference call on Tuesday recapping the firm's 2021 earnings, CEO Brad Gray highlighted several "important CosMx milestones," including a BioRxiv preprint describing the CosMx technology and performance and the release of a dataset mapping nearly 1,000 RNAs in situ at single-cell resolution using formalin-fixed paraffin-embedded samples.
"Together, these releases have created quite a buzz around CosMx," Gray said, underscoring nearly 6,000 downloads of the manuscript and 400 downloads of the National Institutes of Health grant application package for CosMx. According to Gray, NanoString generated 20 CosMx orders in 2021. These orders "demonstrated the highly complementary nature" of the firm's two spatial biology platforms, as 95 percent of the CosMx systems ordered were either bundled with a new GeoMx or sold to an existing GeoMx customer, he said.
CosMx "delivers researchers the ability to check more genes than any other in situ system, with a large panel of over 1,000 genes and the sensitivity to detect even low copy numbers," Anna Berdine, NanoString's VP of marketing, said as she introduced the platform at the company's annual user meeting a day before the earnings call. Additional features of CosMx include its multiomic capability to work across a variety of sample types, including formalin-fixed paraffin-embedded tissues, and the 3D imaging system that can deliver sub-cellular resolution.
Berdine also said CosMx will come with "a broad menu of content options," including off-the-shelf RNA and protein panels, which are customizable with spike-in content to "add up to 50 user-defined RNA targets." In addition, the new platform will offer users the ability to create their own "fully customizable panel," she said, including 1,000-plex panels "designed specifically for single-cell applications such as cell typing and cell-to-cell interaction studies."
To support data visualization and analysis, NanoString is also planning to launch the Spatial Biology Portal, a cloud-based system that will provide "integrated data analysis" for both the CosMx and GeoMx systems with "an intuitive interface," Berdine said, adding that the portal will facilitate collaboration across institutions and provide an integrated view of all results associated with a particular study.
Touting CosMx as the "Hubble telescope of spatial biology" during the meeting, Joseph Beechem, NanoString's CSO and senior VP of R&D, laid out the inner workings of the instrument, including what he described as a "complete data-driven" and "automated" process. According to Beechem, CosMx operates in seven steps, including a rapid low-resolution scan of the entire tissue section, morphology markers and nuclei staining, cell membrane staining, imaging of transcripts of 1,000 targeted genes, cell segmentation using a multimodal approach, allocation of transcripts to single cells, and cell typing and mapping.
In addition to a high-plex RNA panel, Beechem said CosMx offers a high-plex protein panel. While the RNA layer of information offers information about tissue function, he said, the protein panel reveals "absolute tissue architecture."
Beechem also highlighted a CosMx dataset containing about 800,000 cells and 260 million transcripts in FFPE tissues from non-small cell lung cancer, which the company made public in November of last year. Specifically, he pointed out that the data showed CosMx achieved 96 percent efficiency at cell detection independent of the sample RNA quality. "That's the advantage of doing in situ-based chemistry," Beechem said. "Our little hybridization barcodes have no trouble hybridizing to the small, fragmented RNA molecules that are there in the samples."
Despite the promising data, company executives said there is still work to be done to prepare CosMx for launch. CEO Gray admitted that although the company has generated the publicly released data on prototype CosMx instruments "that are working [in] our hands here in Seattle," those prototypes "would not be appropriate to be boxed up and shipped to a customer."
For that, he said the firm still needs to "improve the overall robustness of the system," which includes finalizing the layout and the software interface so that it's easy to use. "That's what represents the predominant amount of engineering between now and launch," Gray said, adding that while NanoString hopes the final product will be "nearly physically identical" to the beta systems, it's the software that is still not "100 percent locked on the system" and needs additional feedback.
"We plan to ship our first beta systems to customers during Q2, allowing us to get feedback on installation, training, and workflow," Gray added. "Around the same time, we use the beta system to expand the capacity for our CosMx Technology Access Program, or TAP, which is currently fully subscribed."
In terms of the launch strategy, Gray said the firm will largely follow "the same playbook" as for the launch of GeoMx. That said, he thinks the two platforms will have a similar trajectory after the launch. With GeoMx, "we were doing 10, 12, and 15 or so [orders] per quarter," he said. "That kind of trajectory is what we would expect for CosMx orders."
To that end, Gray claimed the launch of CosMx will "double the size" of NanoString's spatial biology market, expanding the company to cover "virtually all of the $6 billion [total addressable market] for spatial research." He also believes CosMx will likely bring users with "a broader set of scientific interests than NanoString has historically served" to the company's customer base, judging by the first 20 CosMx orders. "We've been very oncology-focused in the past," Gray said. "But a lot of the CosMx interest is going to come from people who are more traditional single-cell biologists."
However, CosMx will likely not take off unopposed. On Monday, 10x Genomics sued NanoString for alleged patent infringement of two patents licensed by 10x from George Church's lab at the Wyss Institute and Harvard Medical School.
A NanoString competitor, 10x unveiled its Xenium platform for in situ analysis, a spatial platform it has been working on since acquiring ReadCoor, in January. Last month,10x also announced that it will expedite the release of Xenium to the end of the year, instead of 2023.
Gray declined to provide more specifics regarding the lawsuit during the conference call, other than declaring that company officials "have studied the claims and are confident that we do not infringe."