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IsoPlexis Targets New Market Segments With Cheaper, More Flexible Single-Cell Proteomic Systems

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NEW YORK – Single-cell proteomics firm IsoPlexis is looking to expand its market reach with the launch of a lower-priced, smaller-footprint platform and new assay capabilities.

The company also continues to move its technology into the clinic, having identified a blood-based biomarker of response to immunotherapy in melanoma that researchers presented on at the Society for Immunotherapy of Cancer (SITC) annual meeting this month.

Branford, Connecticut-based IsoPlexis announced this month the launch of its IsoSpark system, a smaller, lower-throughput version of its IsoLight single-cell proteomics system that the company expects will help it make inroads with smaller labs and other facilities that may not have the budget or the need for the full-sized system.

Sean Mackay, IsoPlexis' cofounder and CEO, said that the company has placed around 100 IsoLights since launching the system two years ago. Many of these systems have been placed in shared or core facilities on academic or pharma firm campuses, he noted.

"What we are seeing is that there is a desire from smaller labs to have access to the data in real time," he said. "They are looking for a smaller-footprint system. Lower throughput is fine for a lot of the experimentation they are doing, but they want, importantly, to not always have to go to a core with all of their experiments."

The IsoSpark has an 18-inch footprint and can run four chips at a time compared to eight chips simultaneously for the IsoLight system. The platform price is in the mid-$100,000 range, around $75,000 less than the IsoLight, Mackay said.

"The market feedback is that at that price it is more accessible than the IsoLight system, which is thought of as more of a core lab system," he said.

Mackay added that the platform is targeted to the academic and biotech markets, which he said "prefer having more modular, personalized lab systems."

IsoPlexis also launched this month the IsoSpark Duo, which is more targeted to the IsoLight user base, offering the same level of throughput but increased flexibility in that it can run two different sets of chips simultaneously, allowing researchers to profile different cell types in the same experiment. Much of IsoPlexis early work has focused on T cells but more recently the company has branched out to offer assays for profiling other kinds of immune cell and tumor cells.

As the company considered future applications for its technology it received feedback, especially from larger biotech and pharma labs, that researchers wanted this kind of flexibility, Mackay said. "Essentially, there are more concurrent cell types… that these parties want to assay from each sample."

He said the IsoSpark Duo would be priced at a premium to the IsoLight platform due to the increased flexibility.

All of the company's systems 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.

IsoPlexis' lead assay product was a chip for measuring cytokines secreted by T cells, which has seen uptake among CAR-T developers for assessing the functionality of engineered T cells and their impact on patient response. Since then the company has launched assays for measuring the cytokine production of other immune cells including natural killer cells and macrophages and monocytes.

This month, the company launched a chip for looking at 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 is preparing to launch a second chip that measures 20 phosphoproteins and proteins involved in adaptive immunity.

Mackay said the expectation is that these assays will allow researchers to more quickly and comprehensively study how protein signaling is dysregulated in cancer and how these pathways respond to therapy.

"You are able to map out more aberrant pathways," he said. "And you go from [needing] months to interrogate multiple protein points, to sort of days."

California Institute of Technology researcher James Heath, whose lab originally developed the technology underpinning the IsoLight platform, has published work demonstrating the system's potential for phosphoproteomic experiments. In a 2016 study, for instance, Heath and his colleagues found that the platform could detect changes in protein phosphorylation patterns in glioblastoma cells as early as 2.5 days after drug treatment.

Researchers have for years used techniques like reverse phase protein arrays to study protein signaling and responses to therapy. The IsoPlexis panel brings such efforts down to the single-cell level. Firms like NanoString similarly offer single-cell profiling of intracellular proteins and can also provide spatial information.

Mackay said the intracellular panels would help the company move beyond its traditional focus on immuno-oncology and into therapies targeting cancer signaling more broadly. He added that they could also draw users doing discovery biology "where they want to add a layer of proteomic, functional information that they are not getting directly from the genome."

Data from IsoPlexis' platform also figured into a recent presentation at the SITC virtual meeting by the company's collaborator Nektar Therapeutics that found that in 41 previously untreated metastatic melanoma patients, levels of polyfunctional CD8 T cells (defined as cells expressing multiple cytokines) increased in patients who responded to combination therapy of nivolumab and Nektar's bempegaldesleukin IL-2 pathway agonist. Increases in these cell levels were apparent by day eight of treatment, "well before clinical measures of response," the researchers noted.

"Immune profiling, durable response biomarkers, which this is, is a much sought after readout," Mackay said, adding that the company had begun engaging "with firms like CROs and other large players in the CRO and diagnostics market that have interest in leveraging our platform to get these biomarkers."

"We have to do a good job over the next couple of years of providing our system to labs that are equipped to do things like CLIA testing," he said regarding how the company plans to approach the clinical space. "Those labs have the expertise and have done this for years, taking [research] platforms and applying those platforms to the development of tests that they offer."

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