Spatial biology is among the smaller segments of the broader life sciences market. The most recent estimate issued August 6 by Research And Markets, has the market growing over the next seven years at a 10% compound annual growth rate $484.22 million, which would put its value this year at just under $250 million.
The field made its way into the mainstream of genomic science when, under the term spatially resolved transcriptomics, it was unanimously recognized in January by editors of Nature as Method of the Year 2020: “This maintenance of spatial context is crucial for understanding key aspects of cell biology, developmental biology, neurobiology, tumor biology and more, as specialized cell types and their specific organization are crucially tied to biological activity and remain poorly explored on the scale of whole tissues and organisms.
Spatially resolved transcriptomics technology is being applied by large consortia such as the Human Cell Atlas and Brain Initiative Cell Census Network (BICCN), with the ultimate goal of generating complete maps of large and complex tissues like the human brain, Nature also noted.
But to professionals in the specialty, the thrill of spatial biology is less about the numbers, or the recognition from a top-tier journal, than about the discoveries its technologies have made possible.
Two professionals will discuss spatial biology September 9 at a GEN Keynote Webinar, “Spatial Biology Redefines the Multiomics Approach”: Joe Beechem, PhD, chief scientific officer and senior vice president of Research and Development at NanoString Technologies; and Arutha Kulasinghe, PhD, a research fellow and leader of the spatial biology and liquid biopsy group at the University of Queensland’s Diamantina Institute in Australia.
“If you’re looking at an immune response, are those immune cells actually attacking a tumor cell or attacking a cell that is infected with coronavirus? These are things that you can figure out from spatial technologies that you could not figure out from previous technologies,” Yoni Bock, PhD, associate VP of Reagents R&D with Vizgen, said June 16 on “GEN Live,” GEN’s monthly live-streaming video discussion series.
Vizgen is among companies appearing below in GEN’s first-ever top-10 A-List for spatial biology biology—the five largest public companies and five largest private companies. The public companies are ranked by their 2020 revenues as disclosed in regulatory filings, including sales of products or services, as well as revenue from collaborations and R&D activity. Private companies are ranked by the total capital they have raised, as disclosed by the companies themselves, either in press statements or in responses to GEN queries verifying figures compiled by other sources.
Also included in this list are eight “up-and-comers” that have either raised significant capital in recent months, shown positive data for their technologies, and/or launched significant new collaborations with partners.
Each company is listed with a short explanation of their recent activity.
|5. Akoya Biosciences
Revenue: $42.443 million in 2020; $25.283 million in the first half of 2021
Akoya Biosciences went public in April, raising approximately $138.2 million in net proceeds via IPO. Since then, Akoya—which calls itself “The Spatial Biology Company™—has joined microscope providers Nikon, CrestOptics, and Andor to develop new spatial biology applications, and broaden access to Akoya’s CODEX® single-cell multiplexed imaging solution through the I2 Network. Akoya also began partnering with AstraZeneca to advance new multiplex immunofluorescence (mIF) workflows and spatial biomarker signatures based on Akoya’s Phenoptics™ platform, aiming to elucidate the immune biology of cancer. Phenoptics was highlighted in the MITRE study published last month in the Journal for ImmunoTherapy of Cancer, the first multi-institutional analytical demonstration of a spatial biology workflow. And on August 10, Akoya reported a 53% year-over-year Q2 revenue jump, to $13.1 million, though its net loss rose from $4.546 million to $5.569 million.
|4. NanoString Technologies
Revenue: $117.316 million in 2020; $65.48 million in first half of 2021
NanoString Technologies marked a milestone in the second quarter: Its nCounter instrument business achieved its 1,000th placement. NanoString ended the quarter with a $27.02 million net loss (~$100,000 less than Q2 2020) on revenues that climbed 50% year-over-year, to $33.863 million, the company said August 4. Another bright spot: NanoString generated record orders for its GeoMx Digital Spatial profiler (DSP) systems, more than doubling its installed base to approximately 190 systems as of June 30, and launched its Whole Transcriptome Atlases—including the GeoMx Mouse Whole Transcriptome Atlas, designed to provide high throughput RNA profiling in the primary model organism for discovery research. WTA has driven a steady increase in demand for GeoMx consumables since its launch in February at the Third Annual Spatial Genomics Summit.
Revenue: $138.144 million in 2020; $63.812 million in first half of 2021.
Fluidigm’s base business rebounded during Q2, driven by early customer orders for its new fourth-generation CyTOF® XT mass cytometry product, On August 5, Fluidigm inked a co-marketing agreement with privately-held Ultivue, which has raised more than $100 million, through which the companies will offer imaging solutions for biomarker discovery and drug development. In May, Fluidigm joined the FLAMIN-GO Project academic-industry consortium to create an organ-on-a-chip solution for clinical trials in rheumatoid arthritis therapy. For FLAMIN-GO, Fluidigm is using its Hyperion™ Imaging System to provide training, support, and equipment for Imaging Mass Cytometry™ (IMC™) studies at the University of Eastern Piedmont in Novara, Italy. Fluidigm finished Q2 with a $17.143 million net loss (up from a year-ago $14.160 million net loss), though revenue climbed 19% to $31.018 million.
|2. 10x Genomics
Revenue: $298.8 million in 2020; $221.663 million in first half of 2021
10x Genomics maintained its torrid growth pace in the second quarter, with revenues nearly tripling year-over-year to $115.842 million and net losses narrowing to $11.052 million (from $40.167). Last month, 10x launched its next-generation Chromium X Series for single cell analysis, enabling routine million cell experiments to run at 2 cents per cell—an industry first, according to the company. The platform includes Chromium iX, designed for cost-effective, lower throughput single cell analysis, which is upgradable to the high-throughput full-range Chromium X. And in June, 10x began shipping its new Visium Spatial Gene Expression for FFPE (formalin-fixed and paraffin-embedded) assay, giving researchers access to the whole transcriptome across their entire tissue, which the company said enables true unbiased discovery in FFPE samples.
Revenue: $1.988 billion in 2020; $1.126 billion in first half of 2021
Bruker has established a spatial biology beachhead over the past year, in part through a majority investment in Acuity Spatial Genomics, formed in March to advance spatial 3D genomics and multiomic analyses for discovery. Bruker invested $4.5 million, it disclosed in a regulatory filing. Acuity exclusively licenses from Harvard University its technology platform, designed to enable genome-wide visualization of spatially resolved 3D chromatin architecture in individual cells and cell populations in situ. In September 2020, Bruker acquired Canopy Biosciences, whose products and services include spatial biology. On August 5, the University of Pittsburgh added Canopy’s ChipCytometry™ to its Unified Flow Core in the Department of Immunology, to advance high-plex single-cell spatial biology research by quantifying cell phenotypes and their spatial relationships within the native tissue microenvironment.
|5 (tie). Resolve Biosciences and Rebus Biosystems (formerly Optical Biosystems)
Total Capital Raised: €21.5 million (Resolve); $26.5 million (Rebus)
Resolve Biosciences likens its spatial approach to mapmaking, calling its platform Molecular Cartography™ designed to help scientists resolve the most complex biological challenges in areas that include oncology, neuroscience, and infectious disease. The platform, under development since 2016, recently detected specific gene expression patterns in SARS-CoV-2 that were unseen with existing RNA sequencing or single-cell RNA-seq technologies. … Rebus Biosystems launched its Rebus Esper™ spatial omics platform in March to help researchers studying cancer, immunology, infectious disease, and neuroscience. Launched at the Advances in Genome Biology and Technology (AGBT) virtual meeting, Rebus Esper applies Rebus’ Synthetic Aperture Optics (SAO) technology, a super-resolution technique designed to enable routine quantitative analysis of tens of millions of cellular features across hundreds of thousands of cells. In March, Rebus named Neil Kennedy as Chief Commercial Officer and Scott Kothlow as Chief Financial Officer.
|4. Lunaphore Technologies
Total Capital Raised: CHF 38.3 million ($42.3 million)
Bringing spatial technology into mainstream labs studying cancer and other diseases is the goal of Lunaphore Technologies. Last month, the Swiss spatial biology company launched a partnership of undisclosed value with the Institute of Pathology at University of Bern, through which its Translational Research Unit will use Lunaphore’s COMET™ high-multiplexed immunostaining technology to study isolated cancer cell clusters called tumor buds in colorectal cancer. By expanding understanding of tumor budding events, the partners said, they also aim to improve cancer prognosis as well as personalized medicine. The company has also beefed up its boards in recent months, naming Carlo Bifulco, MD, of Providence Cancer Institute to its Scientific Advisory Board, formed in January, and appointing former Leica Biosystems President Matthias Weber to its Board of Directors.
Total Capital Raised: $51 million
Vizgen’s MERSCOPE™ platform is designed to enable massively multiplexed, genome-scale nucleic acid imaging at sensitivity and high-resolution imaging down to 100nm, to capture data scaling from whole tissue section to single-cell and subcellular detail. MERSCOPE aims to offer researchers insights into tissue-scale basic research and translational medicine in oncology, immunology, neuroscience, infectious disease, developmental biology, cell therapy, and gene therapy. A month earlier, Vizgen released the Vizgen MERFISH Mouse Brain Receptor Map, the first of a series of datasets made available through Vizgen’s Data Release Program. Last month Vizgen relocated to a larger facility in Cambridge, MA, and named Bob Koshgarian as Vice President of Operations to develop and manage manufacturing and supply chain strategies. Both moves are intended to support Vizgen’s commercial launch of MERSCOPE.
Total Capital Raised: $52 million
RareCyte says its Precision Biology™ solutions offer multiplexed analysis of cells and tissue for customers performing single cell applications in oncology and disease research to bring new therapeutics and diagnostic assays to market. In June, RareCyte announced a biomarker liquid biopsy assay for the neuroendocrine marker synaptophysin (SYP), designed to help customers evaluate SYP expression on circulating tumor cells (CTCs). The assay entails processing blood to slides with the AccuCyte® Sample Preparation System followed by staining with the RarePlex® 0920-VB Synaptophysin CTC Panel Kit, enabling blood-based investigation of a prominent mechanism by which tumors become resistant to second-line endocrine therapies. The assay includes imaging on a CyteFinder® Instrument, RareCyte’s first commercial product released in 2015. Three years later, RareCyte moved into its 22,000-square-foot lab/office facility in Seattle.
Total Capital Raised: $100 million+
With the addition of new executive team members in 2021 and over $100 million of funding raised to date, Ultivue has targeted spatial biology innovation to support much-needed biological insights from solid tumors. Its customers address the challenge of therapeutic response rates in patients undergoing immunotherapy using a bespoke kit-based approach that enables multiplex biomarker assays for tissue phenotyping and digital pathology. The company’s proprietary InSituPlex® technology is designed for quick and comprehensive exploration of biologically relevant markers combined with same slide-H&E analysis to provide more data from precious tissue samples. The entire assay can be run manually or on multiple different commercially available hardware platforms to support academic, biopharma, and CRO customers. On August 5, Ultivue inked a co-marketing agreement with publicly traded Fluidigm, wherein the companies will offer a translational workflow solution for biomarker discovery and drug development.
|Advanced Cell Diagnostics (ACD)
When Bio-Techne acquired Advanced Cell Diagnostics (ACD) in 2016 for up to $325 million, it envisioned expanding into genomics technology, as well as within clinical labs. In the years since, one way ACD has helped Bio-Techne fulfill those goals has been through spatial biology, where the company last month expanded its RNAscope™ HiPlex platform, an advanced, in situ hybridization (ISH) tool created to understand vital gene expression patterns at single cell resolution. RNAscope HiPlex v2 is designed to generate precise gene expression data, enabling comprehensive spatial studies from 12 targets in FFPE samples and up to 48 targets in Fresh and Fixed Frozen sample types. A major application for the RNAscope HiPlex Assay, according to ACD, is validating gene signatures with spatial context at the single cell level.
Dovetail Genomics, an EdenRoc Sciences company that specializes in high-quality de novo genome assembly, announced a partnership August 9 with Revive & Restore, a wildlife conservation organization promoting the incorporation of biotechnologies into standard conservation practice. Through its Wild Genomes program, Revive & Restore agreed to fund high-quality de novo genome assembly for select species where an immediate, practical application of genomic data can inform and improve conservation efforts. Dovetail Genomics was named the preferred de novo genome assembly provider, building on its delivering over 1,600 plant and animal assemblies to hundreds of researchers worldwide for nearly a decade.
Ionpath won a key legal victory in February, when the US District Court for the Northern District of California decided IonPath’s MIBIscope™ technology did not infringe on patents of Fluidigm—which vowed to appeal the ruling. MIBI stands for “Multiplexed Ion Beam Imaging.” MIBIscope is an imaging platform designed to enable comprehensive phenotypic profiling and spatial analysis of the tissue microenvironment, including novel insights into disease state, mechanism of action, and patient response. Ionpath said MIBIscope lets researchers visualize over 40 markers simultaneously with subcellular resolution down to 280 nm. The company completed an $18 million Series B financing in September 2020, with investors that included Bruker.
Single Technologies, whose 3-D sequencing technology is designed to enable both spatial and next-generation sequencing, brought its total capital raised to €5 million (about $6 million) in December 2020 by completing a heavily oversubscribed financing. Single was founded in 2014 following research in single-molecule imaging and biotechnology applications at Stockholm’s Royal Institute of Technology (KTH) combined with R&D in fiberoptic grating by founders of Proximion. Single raised a SEK15 million ($1.7 million) convertible loan last year. CEO Johan Strömqvist has said Single aims to open its first data sequencing production site in Stockholm by 2022.
Singular Genomics recently completed an IPO that raised approximately $237.2 million in net proceeds. Approximately $50 million in proceeds will fund product development and commercialization of its PX Integrated Solution, which combines single cell analysis, spatial analysis, genomics and proteomics in one integrated instrument designed to provide a versatile multiomics solution. Singular stated in its IPO prospectus that it anticipated a 2023 commercial launch for PX, the company’s second product in development (the first is the G4 Integrated Solution, a benchtop next-generation sequencer). A new manufacturing facility in La Jolla, CA, is being built out to support manufacturing of PX and G4.
S2 Genomics, a manufacturer of automated tissue sample preparation systems, last year launched the Singulator™ 100 System, designed to automate the processing of solid tissue samples into suspensions of single cells or nuclei with high yields and from small samples for a wide range of single-cell biology and genomic analyses. The company followed up on its launch through distribution agreements with partners in Asia-Pacific, Canada—and most recently, Europe (with GC Biotech of The Netherlands, announced in July). S2 is also partnering with the RIKEN Center for Integrative Medical Sciences to evaluate the performance of the system and develop new applications for Singulator.
Veranome Biosystems, an Applied Materials company, agreed in June to integrate its instrument and analytics with Portal Bioscience’s highly specific, probe ligation-based Proxal™ chemistry to deliver spatially resolved analyses of shorter RNA molecules with tracking of subtle sequence differences due to splicing or mutation. The partnership, whose value was not disclosed is intended to enable tracking of fragmented RNA often found in FFPE specimens, as well as detect mutations, gene fusions and splice variants. Veranome says its end-to-end multi-omics solution combines genomics expertise with world-class high-speed diffraction limited optical imaging capabilities adapted from the field of semiconductor inspection.
|Visikol, a CELLINK Company
Visikol provides biopharmas with contract research services that include 3D cell culture, 3D tissue imaging, multiplex imaging, and digital pathology services. Hampton, NJ-based Visikol was acquired in May for $7.5 million cash and stock by Swedish-based CELLINK, the parent of 11 companies encompassing “bioconvergence” of biology, engineering, big data and AI (CELLINK shareholders have approved renaming the company as BICO later this month). Founded in 2016 by entrepreneurs from Rutgers University, Visikol counts half of the top 20 biopharmas as customers, and provides in-depth analysis of tissue and cell culture samples through its 3Screen™ software platform, built on advanced machine learning evaluation.
*This table was updated and Ultivue was added on August 17, 2021.