10x Genomics has begun commercial shipping of its long-awaited Visium HD Spatial Gene Expression instrument this week, a next-generation version of the company’s Visium spatial biology tool, two years after first announcing the technology.

Visium HD is designed to allow users to comprehensively characterize FFPE tissue sections by measuring whole transcriptome spatial gene expression at single cell-scale resolution. The new tool can detect 11 million features in a continuous grid-pattern of 2 μm squares, compared with just 5,000 features detectable in a hexagonal arrangement of 55 μm spots for 10x’s widely used, slide-based Visium Spatial Gene Expression.

“You were seeing interesting patterns before. But now you’re really able to go zoom in and understand things in a lot more detail, and things that were kind of getting averaged out before,” Michael Schnall-Levin, PhD, 10x’s founding scientist and chief technology officer, told GEN Edge. “This is going to allow people for the first time ever in the world to do things like take an FFPE tissue, and measure basically every gene in the human genome, where that’s turned on at single cell resolution. We think it’s really exciting new capability, and we’re really excited to get that into customers’ hands.”

A side-by-side comparison of Visium data (left) and Visium HD data (right) in FFPE human colorectal cancer. The new tool can detect 11 million features in a continuous grid-pattern of 2 μm squares, compared with just 5,000 features detectable in a hexagonal arrangement of 55 μm spots for 10x’s current version of Visium. [10x Genomics]

Like its current-generation version, Visium HD is FFPE compatible, Schnall-Levin said. Visium HD can generate data from human or mouse FFPE samples, including archived blocks or pre-sectioned slides, using a universal sample preparation protocol.

Other new features of Visium HD:

  • Sequencing-based spatial transcriptomics data: Users can map gene expression more precisely than before by using a workflow exclusively available on Visium CytAssist, which the company characterizes as best-in-class.
  • Enhanced histology: Visium HD can integrate hematoxylin and eosin (H&E) or immunofluorescence (IF) images with high-resolution spatial transcriptomics from the same tissue section.
  • Analysis and visualization tools: Users can seamlessly combine histological and gene expression data using updated versions of SpaceRanger (v3.0) and Loupe (v8.0), with the goal of enabling intuitive data exploration and accelerating discovery.

As of December 31, 2023, 10x had sold 531 Visium CytAssist instruments, about 9% of the total 5,966 instruments sold by the company since it was founded in 2012. More than 2,900 labs worldwide have used Visium since its launch in 2019 as an instrument-free workflow as the Visium Spatial Gene Expression assay.

Visium HD is list-priced at about $12,500 for a 4-reaction kit, which is about 1.75x the list price of the current Visium on the market, Visium CytAssist. Launched in 2022, Visium CytAssist was developed to help streamline the Visium workflow by allowing expanded sample access, simplifying sample handling, and improving data quality for spatial transcriptomic studies.

10x has not disclosed any projections on Visium HD’s sales revenue, or number of instruments it expects to sell.

Manufacturing challenge

10x first announced plans for Visium HD at its Xperience 2022 product showcase, and promoted plans for the next-gen instrument at last year’s Advances in Genome Biology and Technology (AGBT) conference. “Early-stage experiments show Visium HD’s ability to resolve tumor borders in human breast cancer cells, and provide resolution that identifies cellular composition of layers in a mouse eye,” 10x posted on its blog at the time.

The company hadn’t been able to start commercial shipping of Visium HD until now, because it needed to accelerate scaling up of manufacturing for the instrument—a challenge it surmounted through an acquisition completed last year of intangible and other assets relating to an intellectual property license from Centrillion Technologies and parent Centrillion Technology Holdings.

Centrillion has since granted 10x a license enabling manufacture of Visium HD. According to its Form 10-K annual report for 2023, 10x has paid Centrillion a total $61.3 million since last year. That consists of $10 million in upfront cash, then an additional $10 million cash in July 2023 when the deal was closed, plus additional cash tied to achieving milestones. 10x paid Centrillion $21.3 million in December for completing development milestones, plus another $20 million in January for achieving a development milestone.

The company has agreed to pay $15 million more if it achieves an additional technology development milestone, then additional cash tied to reaching future sales milestones.

Speaking with GEN Edge in January, 10x co-founder and CEO Serge Saxonov, PhD, said Visium HD was the most requested product in the history of the company, which as a result expects to add new Visium customers to its base of existing ones.

“The dominant fraction [of Visium HD customers] should be existing customers for Visium. But also importantly, a lot of other customers have been sitting on the sidelines waiting for this resolution capability to come along because that was what the big quest has been, so we are pretty excited,” Saxonov said. “It’s pretty clear to us that this will drive a material expansion of the Visium market. How much? Well, we’ll have to see, but it is a huge, huge jump in our capabilities, and it’s precisely what customers have been asking for.”

Spatial growth potential

10x has not broken out sales for Visium, instead combining them with sales of its Xenium In Situ single-cell spatial imaging platform in a category called “Spatial.”

The Spatial category’s instrument revenue rose nearly 5.5-fold last year, to $75.605 million from $13.844 million in 2022. The 2023 instrument revenue figure includes $27.248 million generated in Q4. Consumables revenue for Spatial products rose 68.5% in 2023, to $59.237 million from $35.155 million two years ago. More than one-third (37%) of 2023 consumables revenue ($22.17 million) was garnered in Q4.

Both Visium and Xenium revenues pale in comparison to those of 10x’s oldest and most lucrative of its platform technologies, the Chromium Single Cell Immune Profiling platform launched in 2016. Last year Chromium generated $58.552 million in instrument revenue, up 22% from $47.866 million in 2022—as well as $420.316 million in 2023 consumables revenue, up 5% from $400.433 million the previous year.

“Spatial seems like it has more growth potential,” Nava Whiteford wrote in his ASeq Newsletter, a Substack publication.

10x began offering researcher customers early access to Visium HD in January, soon after Saxonov revealed plans to begin commercial shipping of the next-generation Visium instrument among a series of announcements during his presentation at the 42nd Annual J.P. Morgan Healthcare Conference.

“Mind blowing, batshit crazy stuff coming soon…” enthused Luciano Martelotto, PhD, head of the development laboratory of the Adelaide Centre for Epigenetics (ACE), South Australia ImmunoGENomics Cancer Institute (SAIGENCI), in a March 25 post on X, formerly Twitter. He offered thanks to 10x using the praying-hands emoji, and added emojis for a kiss, a heart, and a smile next to the letters “HD.”

“When I first heard about it, I knew it was gonna be a game-changer!! Can’t wait to see what the data looks like!” replied Givanna Putri, PhD, a postdoc in the lab of Belinda Phipson, PhD, at WEHI (Walter and Eliza Hall Institute) in Australia.

Nadav Yayon, PhD, a postdoctoral fellow in the labs of Sarah Teichmann, PhD, at Wellcome Sanger Institute; and of John Marioni, PhD, and Virginie Uhlmann, PhD, both visiting group leaders at EMBL-EBI, used Visium HD to showcase “innovative techniques that are pushing the boundaries of what’s possible in the field,” during a talk highlighting the impact of AI on stem cell research and medicine.

Two primary competitors

Visium HD is competing primarily with instruments from NanoString Technologies and Curio Bioscience, Albert Vilella observed in December in his Rhymes with Haystack, a Substack publication that covers spatial biology and other biotech technologies.

NanoString last month commercially launched the CosMx™ Human 6K Discovery Panel, which according to the company is the industry’s first single-cell spatial panel enabling research scientists to carry out RNA assays enabling analysis of up to 6000 genes from a single slide, representing nearly every human biological pathway.

“NanoString offers multiple panels for CosMx, harnessing its capabilities for researchers in oncology, neuroscience, infectious disease, immunology, and developmental biology,” NanoString president and CEO Brad Gray told GEN Edge.

CosMx Human 6K Discovery panel was developed for NanoString’s CosMx Spatial Molecular Imager (SMI), which can analyze gene expression profiles of 1,000 transcripts of RNA and 64-plex proteins in a single experiment—which had been the highest highest-plex multiomic imager available, NanoString technical writer Geoffrey Hummelke, PhD noted last year in GEN.

In January, NanoString announced it had obtained the first public dataset of the whole transcriptome obtained at true single-cell resolution using CosMx SMI, a single cell spatial biology feat that allowed researchers to simultaneously visualize the expression of every protein-coding gene in the human genome in situ.

“CosMx™ Spatial Molecular Imager (SMI) provides true single cell RNA and protein imaging with the most precise cell segmentation and highest plex available,” Gray said.

Next year, NanoString plans to commercially launch its CosMx Whole Transcriptome Panel, which is also designed to extract insights from FFPE tissue samples—and which can image the expression of almost 19,000 genes at once.

The company last September launched its GeoMx IO Proteome Atlas (IPA), a spatial proteomics assay for the GeoMx® Digital Spatial Profiler (DSP) that is designed to enable spatial profiling of more than 500 immuno-oncology relevant targets from FFPE tissue sections.

First data

Two months later at the 38th annual meeting of the Society for Immunotherapy of Cancer (SITC) in San Diego, E. Aubrey Thompson, PhD, of the Mayo Clinic and Amaya Pankaj, MBBS, a research fellow from the lab of David Ting, MD, at Massachusetts General Hospital, shared the first data from GeoMx DSP. Thompson shared a comparison of early-stage HER2+ tumor biopsies from patients, both responders and non-responders to neoadjuvant treatment, while Pankaj presented on the dissection of pancreatic tumor cells by harnessing spatial multiomics using GeoMx IPA for protein and another NanoString product, the Whole Transcriptome Atlas for RNA.

We believe that scientists benefit from access to multiple spatial biology platforms, enabling them to select the approach that is best for their specific experiment and most aligned with the questions they seek to answer with their research,” Gray added.

NanoString delisted its shares from Nasdaq and began trading its shares on the Over-the-Counter market in February after filing for Chapter 11 bankruptcy. The company, joined by three of its subsidiaries, filed for protection from creditors under Chapter 11 of the U.S. Bankruptcy Code, with NanoString blaming the filing on a $31 million jury award assessed against it last November in a patent infringement case filed by 10x in U.S. District Court for the District of Delaware.

NanoString is appealing the jury award, which held that NanoString’s GeoMx® Digital Spatial Profiler (DSP) infringed seven patents that 10x held after exclusively licensing them from Prognosys Biosciences. NanoString has since agreed to be acquired by the healthcare investment firm Patient Square Capital for $220 million, in a deal that requires approval by the U.S. Bankruptcy Court.

Curio’s Seeker Spatial Transcriptomics Kit is designed to enable whole transcriptome, spatial mapping of fresh frozen tissues for any eukaryotic organism at 10 μm resolution (making Curio first to reach single cell resolution), using a packed monolayer of beads designed to delivers a continuous view of a cellular region of interest. According to Curio, the assay plugs directly into existing sequencing workflows and requires no new specialized instrumentation or novel probe sets.

Curio has signaled that it plans to come out with an instrument for FFPE tissue samples by the end of 2024.

Portfolio expansion plans

Earlier this month, Curio unveiled plans to expand its portfolio by announcing an early access program (EAP) to test its latest product Trekker, a commercial version of its slide-tag technology developed by researchers from the Broad Institute of MIT and Harvard and published in Nature this past December.

Trekker, which aims to bring spatial data to the single cell genomics market, would be Curio’s second commercial product after Seeker, which like Trekker was developed in the academic labs of Broad Institute researchers Evan Macosko, MD, PhD, and Fei Chen, PhD.

As of November 2023, privately-held Curio reported having over 100 customers using its technology.

“TXG will have to rethink how much discovery people want to do on their Visium line versus the Xenium, and gauge the threat that Curio Bio is to their Visium product line,” Vilella wrote on February 16.

Visium HD is 10x’s fourth new product to begin shipping to customers during the first quarter. 10x also began commercial shipping of the first two products powered by its new GEM-X technology architecture, the Chromium GEM-X Single Cell Gene Expression v4 and its GEM-X Single Cell Immune Profiling v3 assays; and began marketing the first of four planned new offerings for its Xenium platform, namely systems with improved cell segmentation capability.

During the second quarter, targeting midyear, 10x expects to start shipping for Xenium customers 5,000 Plex gene expression panels; followed during the second half by in-line multiplex protein detection; then 1,000 and 2,000 Plex Panels, which are set to start shipping later this year or early 2025.

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