NEW YORK – Fresh off a $125 million initial public offering, single-cell omics firm IsoPlexis is looking to move beyond its roots in protein analysis into areas including transcriptomics and metabolomics.
Last month at the Advances in Genome Biology and Technology Precision Health meeting, the Branford, Connecticut-based company presented proof-of-concept data from its new Duomic platform, which allows single-cell transcriptomic and proteomic measurements. It is also working on adding metabolomics to its offerings using technology licensed from the lab of James Heath, president of the Institute for Systems Biology and a member of IsoPlexis' board.
With these new technologies, the company aims to expand beyond its traditional focus on immuno-oncology into other areas of drug development as well as more discovery-oriented research, said cofounder and CEO Sean Mackay.
IsoPlexis launched in 2014 as a spinout from the lab of Rong Fan, associate professor of biomedical engineering at Yale University. The technology underpinning the system was originally developed in the lab of ISB's Heath, then a professor at the California Institute of Technology, where Fan was a postdoc.
The company's lead products are its IsoLight and IsoSpark systems, which use microchips featuring arrays of thousands of microchambers that isolate individual cells from samples of interest. These chambers are then sealed with a slide patterned with groups of antibodies in a number of different spatially isolated lines. This allows the researchers to identify proteins based on the color of fluorescence produced upon binding and the location on the slide where the binding event occurs. In this way, they can multiplex well beyond the levels allowed by fluorescence readout alone.
In its initial work, IsoPlexis has focused heavily on measuring cytokines produced by engineered T cells to assess their likely effectiveness as drug products. The company offers a 32-cytokine panel targeting this application.
Last year, the firm launched a chip for measuring intracellular proteins at the single-cell level. It currently has one chip on the market measuring 15 phosphoproteins and proteins involved in tumor signaling and plans to launch a second chip that measures 20 phosphoproteins and proteins involved in adaptive immunity.
At AGBT Precision Health, the company presented data on its Duomic platform, demonstrating that using barcorded beads, it could read out transcriptomic data on the same chips it uses for its intracellular protein measurements.
"From those same cells that you are getting the [RNA] sequencing information, you are getting functional proteomic information," Mackay said. He added that the Duomic product would work with any downstream sequencer.
He said IsoPlexis believed the Duomic platform would help the company and its customers better understand what the genetic drivers of cellular activity are at the protein level. While a number of companies offer combined RNA and protein measurements at the single-cell level, most of these offerings focus on characterization of cell surface proteins. Mackay said he believes IsoPlexis' ability to look at secreted and intracellular proteins, including phosphorylated proteins, will set it apart.
"We're really focused on continuing [to develop] our functional proteomic [tools], looking at cytokines, chemokines, growth factors, and the RNA concurrently from things like immune cells, and looking at those same analytes and things like phosphoproteins and RNA concurrently in things like tumor cells," he said. "That's our real differentiating factor, driving the functional proteomic elements."
Mackay noted that as part of this push into nucleic acid work, the company purchased in May a patent portfolio containing 86 patents related to RNA and DNA sequencing.
Currently, IsoPlexis is running Duomic samples in house for a set of early-access users, Mackay said, but ultimately customers will use the company's IsoLight or IsoSpark systems to run the Duomic chips, collecting the protein information, and retrieving the RNA, which they would then sequence.
Mackay said IsoPlexis' metabolomic assay, which is still under development, is meant to be combined with its phosphoproteomic assay, allowing researchers to simultaneously collect information on protein signaling within a cell and its energy state.
"Those two things feed off each other," he said. "Our goal is not to come out with a full-fledged, pure-play metabolomic assay but instead to do the metabolome and phosphoproteome concurrently."
As IsoPlexis continues to develop intracellular protein assays, it expects to move beyond the immune profiling space where it has primarily operated, Mackay said, and into research areas where it will aim to displace technologies like traditional western blots.
"If you look downstream at some of these other applications like phosphoproteomics, if you look today at what academics and small-molecule pathway-oriented drug developers look at, a large portion of it is done with western blot," he said. "And if we can offer highly automated single-cell and bulk alternatives to western blot, that becomes very powerful. That's why we're investing pretty heavily in that part of the business."
"It's a totally different customer set relative to the immune profiling customer that we typically have for cancer immunology, CAR-T, and inflammatory disease," he added.
IsoPlexis generated full-year 2020 revenues of $10.4 million, up 39 percent year over year from $7.5 million. Its net loss for 2020 was $23.3 million versus $13.6 million the prior year. As of June 30, it had placed 150 of its systems globally in total. Mackay said that it planned to use the proceeds of its IPO to "double down" on its sales effort, "particularly in the international regions where we can offer more support to customers now that we're able to hire more people."
He said the company, which has more than 300 employees, has seen strong growth in the EMEA region and recently built an Asia-Pacific commercialization team, which will focus on China.