IsoPlexis CEO and co-founder Sean Mackay

Robert Hooke’s initial discovery of the cell in 1665 has given way to many of today’s scientific and clinical advancements. The field of single-cell biology has come a very long way from the first microscopes of centuries ago to today’s omics-oriented instruments, algorithms, and molecular tools, which continue to lay the foundation for the medical innovations of tomorrow. And although we can now peer into the inner workings of cells through the lenses of many families of biomolecules, there is not only a race to measure, decode, and interpret cellular complexity but to provide the platforms to do so.

IsoPlexis (NASDAQ: ISO) is a life science technology company building solutions to reveal unique biological activity in small subsets of cells, enabling researchers to connect more directly to in vivo biology and develop more precise and personalized therapies. The seamless, hands-off workflow and automated analysis of IsoPlexis’ instrumentation is designed to deliver actionable ‘omics data to accelerate pathway discoveries while bridging them to real-time, in vivo biological activity.

In addition to offering single-cell solutions for measuring proteomes, metabolomes, and (the dubiously named) secretomes, the Connecticut-based company in early September unveiled its multi-omic solution Duomic, which simultaneously measures functional protein and gene expression levels from the same cell.

This release took place just a few weeks before the company announced the closing of its initial public offering (IPO) of 8.333 million shares of common stock at $15 per share ($124,995,000 for the total size of the offering). The quiet period for IsoPlexis (during which insiders and underwriters involved in the IPO are restricted from issuing any earnings forecasts or research reports for the company), expires on November 17, 2021. Following IsoPlexis’ quiet period, brokerages that served as underwriters on the stock are expected to initiate research coverage on the company.

GEN Edge met with CEO and co-founder Sean Mackay, a graduate of Yale’s School of Management, on the IPO closing date (October 8, 2021) to discuss the guiding concepts that have driven IsoPlexis to the forefront of single-cell technology.

GEN Edge: What were the founding mission and vision of IsoPlexis, and how has that changed since the company’s inception?

Mackay: We started IsoPlexis back in 2014. We had been working with academic co-founders at Yale and Caltech. I had seen an initial academic prototype where you could get precise information about important cells while developing a cell therapy, such as TCR therapy or CAR-T therapy. At the time, utilizing immune therapies and engineered cell therapies as drugs was very nascent. So, I was going out to investors and telling them, based on a powerful use-case, that we have this tech that detects significant subsets of cells for developing medicines, and we’re going to play a big part in figuring out which of these sorts of advanced medicines are better.

The question at the time was: are cell therapies like cancer immunotherapies going to be a mainstay? At that moment, there were zero cell therapies approved, and cancer immunotherapies were having a really tough time during the 2000s. So, you had to believe two things: that immunotherapies would be large and deliver curative, long-term responses, and you had to believe that our tech was well suited to capture the important info to do so.

What has been exciting is the trajectory of cancer immunotherapies (two of the top three oncology drugs in the world right now), CAR-T, cell therapies, and gene-edited therapies. It’s exciting that we’ve been part of the process to ride that wave and help push it forward. I think it was hard for anyone other than hardcore clinical scientists to imagine that therapeutics would’ve gone as quickly the last five years and that single-cell technology would have advanced as far as it has. It’s been an incredible journey, but I still think it’s just the beginning.

GEN Edge: Why did IsoPlexis choose to create a comprehensive product suite, from instrument to consumables, and provide customer support and collaboration?

Mackay: There were a couple of elements we were inspired by. At the beginning of the single-cell revolution, some of the big players in these spaces worked with academic researchers to develop a slew of killer applications like single-cell gene expression and immune profiling followed by ATAC-Seq to the single-cell spatial biology world. As we grew, we worked with many key opinion leaders pretty early and looked into what was needed to advance the functional proteomics side of research that single-cell genomics doesn’t have or can offer. We knew we needed to be special because you can’t really compete with the big behemoths if you don’t offer something new and special, whether it’s flow cytometry or single-cell genomics.

What ended up happening is that there was this slew of requests to see what you could do. One was a need to assay not just T-cells but all types of cell types throughout the body. That told us that we had to develop proteomic panels and look at the functional proteins and the phosphoproteomic profiles intracellularly. Over time with our co-founders, we developed methods to do both of those.

The last thing pertains to the industrialization aspect. We can offer a bunch of panels to analyze a bunch of different cell types; but what everyone wants is full automation, which is not trivial. When we started, we thought that was going to be a tough ask. We kept coming up with small innovations between 2014 and 2018 such that when we went from basically running a service to launching the system. We were able to offer a fully automated proteomic workflow that has evolved since then to becoming completely automated in two benchtop instruments as well as analytically automated.

Many people like to do their own informatics. It’s become this cottage industry where you have many experts worldwide who work with some open-source technology and countless informatics people. We saw an opportunity to offer push-button analytics. That ended up being important for us. We envisioned that pharma and biotechs would be big users of our tech right away. That is largely played out, but they weren’t going to want to hire a bunch of informaticians because it’s very different from academics. We really focused on automating the analytics, which we still do to this day, and that has paid off for us. We had to do certain things because we knew that pharma and biotech would not love it if there were various open-source software to navigate and figure out.

GEN Edge: Will IsoPlexis create products intended for clinical use?

Mackay: We have had multiple partnerships around COVID. During the first part of the pandemic, you needed to get fully automated PCR tests to people, which we couldn’t participate in. But the second part of it was to analyze patient samples and figure out what COVID does to people. Now we’re seeing a lot of this new information using our tech and other people’s tech where there are all these different types of patient responses that are driven off different evolutions of the immune system. Partnering around COVID, cell manufacturing, and clinical studies produces lots of data and real business cases for us. What we’ve seen now is that all those partnerships have made us very clinically oriented.

We’re still a research use only (RUO) product, but much of what we’re doing is directly applied in clinical studies. In the last few months, we’ve had several publications for CAR-T and a Phase II clinical study. In all of those studies, if you look at the quotes around the use of our technology, the functionality of our platform is key to engineering iterations for CAR-T studies and biomarker analysis to predict survival that trumped genomic sequencing and flow.

So, while it’s RUO, so much of what we’re doing is being directly applied in clinical studies. That becomes a great leading indicator of how people are going to use this for the next year. It’s probably the best currency we have to communicate the value of our tech, which is that it is highly clinically relevant.

Because of the studies that we’ve done so far, there are direct long-term clinical applications for what we do. We plan to continue down that path and work with our partners. We’ve stated publicly that one of our long-term and larger addressable markets is companion diagnostic work around new therapies and precision medicine where you’re getting product readouts from cell therapies pre-infusion and post-release that are more predictive of the in vivo response. While right now we’re an RUO platform, some of the long-term benefits are really how we get to leverage powerful biology for real clinical usage.

GEN Edge: What sets IsoPlexis apart from other single-cell omics companies?

Mackay: The throughput capabilities that companies are going to have around protein sequencing are very exciting. Bulk proteomics and protein sequencing are in their early days. When you start getting the throughput capabilities and seeing the types of interactions with tens of thousands of proteins simultaneously, that’s going to do a lot for us as a business because it benefits drug development and translational research. If you think of the evolution of genomics, you have so many applied genomics platforms paving the way for single-cell genomics, so it was an intuitive thing to do.

For us, technically, what we’ve done well over the years is that we’ve continued to improve upon this idea of maintaining mid-multiplex for proteomics but doing it in high throughput with single cells. One of the improvements made is going from 90 to 3,000 cells concurrently and how different that is for the research. If you look at how most people are applying proteomics other than us for single cells, it’s extremely laborious and takes weeks to get a sample. It’s non-trivial to take an amazing bulk platform like a mass spec and make it single cell. That’s really where we’re going to continue to stand out.

Frankly, I’m excited about proteomic sequencing. Without revealing future plans, we’ve found ways to work with folks and make some acquisitions to do concurrent sequencing and sample prep with proteomics. So, we envision that as bulk proteomics sequencing becomes a real thing in labs, that there are ways to partner with those guys to contribute to the whole ecosystem. We’re just excited about the proteomics space! As long as we maintain that single-cell differentiation, that’s going to be good for all of us.

GEN Edge: What is the trajectory for IsoPlexis going forward?

Mackay: We have to continue the commercial trajectory we’re on for the following year. We grew about 103% in the first half of the year. Our job here is to continue moving our installed base forward at that clip and investing in the commercial team. There’s a strong need from a customer base. So, in a fast-growing market, our job is to continue that proliferation. Also, our consumable pull-through has gone up a lot. We have to put numbers on the board and continue to show that our customer base is in high demand for our product and continue to show revenue, commercial and operational growth.

In the three-year timeframe, we are going to focus on a couple of exciting products suites. The published literature highlights supercharged subsets of cells revealed by our Duomic product. We’re focused on making that a core part of the sort of multi-omic continuum. We think there are some great multi-domain products and that this is going to be a unique and great multi-domain product, especially for cell types like tumor cells and immune cells that are functionally driven. That’s going to be a big investment as we attempt to launch that in 2023. We’re currently introducing data at various conferences around that.

There’s a recognition that some of the automated solutions we offer are important. We’re taking stock in the market and evaluating what we can also do both for single-cell and bulk proteomics. We started offerings in some bulk proteomics systems that we’re going to invest in next year. We have some very excited customers about the unique sort of profile provided by our product. We have to continue to execute, see those publication trajectories continue to go up, and deliver on our promise.

GEN Edge: How does going public affect IsoPlexis?

Mackay: When you’re able to go public and can access a wider capital-market base of investors, there’s a few degrees of freedom you have now. Of course, we still have to perform and beat our revenue projections. It offers us access to further capital regularly as we continue to develop a vast investor base, and that’s important as we grow. Assuming we continue to grow at this pace, we want to put fuel into the tank for us to continue forward at a high trajectory.

When you’re in the public market, your profile continues to increase as a company. You have the ability to continue to recruit the larger number of people that you need to recruit. And we’ve been able to act very strategically. We’ve managed partnerships and made acquisitions because we’ve been able to grow our investor base while growing our customer base.

This has been an incredible journey. But it’s just early innings. We believe in single-cell biology and multiplex proteomics. It’s great to see that therapeutics are reaching their potential and that single-cell biology is a real thing that’s here to stay.

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