Pieter van Rooyen, PhD, Founder and CEO of Pleno

Can technologies from the industry that put smartphones in nearly everyone’s hands help bring multiomics tools into every commercial and academic lab?

Pleno thinks so. The San Diego startup has developed a platform that applies signal processing techniques derived from telecommunications toward the detection of biological targets for biomedical research and clinical testing. The technology is intended to enable a wide variety of applications that include screening and detection, diagnostics, and prognostics.

Pleno’s Hypercoding™ technology is designed to deliver DNA, RNA, methylation, and proteomic content, among examples of ultra-high plexity (high number of targets) multiomic biological information. Hypercoding can detect up to 10,000 targets per sample and process up to 10,000 samples per day, through a workflow the company describes as simple and low-cost.

“That’s where the telecommunications world meets biochemistry,” said Pieter van Rooyen, PhD, Pleno’s founder and CEO. “We basically think of it as putting a number of cell phone users together—which is, of course, these known targets. Then we encode them and do the detection to determine if that specific target or code is in the sample.”

van Rooyen began his career as an academic researcher focused on electrical engineering before transitioning into entrepreneurial roles founding companies and developing and commercializing their technologies for industries ranging from retail automation and image processing to semiconductors, wireless, healthcare, life sciences, and genomics.

In the life sciences, van Rooyen founded Edico Genome, a developer of data analysis acceleration solutions for next-generation sequencing (NGS) that was acquired by Illumina for $100 million in 2018. Edico’s DRAGEN (Dynamic Read Analysis for GENomics) technology platform was designed to enable a wide range of genomic data analysis, including mapping, alignment, duplicate marking, and haplotype variant calling.

Founded in 2013, Edico emerged from stealth a year later with a $10-million Series A led by Qualcomm’s venture investment group. Investors drawn to Edico included Gregory T. Lucier, who joined less than a year after leading Life Technologies, where he was Chairman and CEO, to a $11.4 billion acquisition by Thermo Fisher Scientific in 2013.

Lucier, now the CEO of healthcare investment firm Corza Health, has teamed up with van Rooyen again—this time, as Pleno’s chairman as well as an investor in the company’s recently-announced $15 million in pre-Series A financing. That financing was raised by an investor group that includes Medical Excellence Capital, an early-stage life sciences venture fund, and Alexandria Venture Investments (the venture arm of Alexandria Real Estate Equities).

van Rooyen and Gavin Stone, VP of Product Development, discussed the launch of Pleno, its technology, and its plans for commercial growth with GEN Edge. (This interview has been lightly edited for length and clarity).

GEN Edge: How long did the $15 million pre-Series A financing take to raise?

van Rooyen: We started at the beginning of last year, and we raised first a convertible debt round early on, the first three months. Then, we raised the rest through the year. I wouldn’t say it took too long.

GEN Edge: How much did the recent downturn in the markets affect the financing?

van Rooyen: I think it’s probably going to eat startups and funding, probably later in the year and next year. That’s why we are raising money as we speak, through our Series A as well. We will make an announcement on that hopefully soon.

GEN Edge: With that financing, how long of a runway does that give Pleno?

van Rooyen: Together with the Series A, we will be able to go probably until the end of next year.

GEN Edge: Pleno specializes in developing multiomic instruments for detecting potential targets through Hypercoding, which you say is a game changer for biomedical research and clinical adoption of applications. What’s so revolutionary about it?

van Rooyen: There’s a couple of things. The first one is the market opportunity that’s available now. For many years, there’s been a lot of sequencing done where people have discovered new targets. The number of applications is really starting to become quite substantial. Some of those very important applications are early cancer screening, NIPT (noninvasive prenatal testing), synthetic genomics, and synthetic ways of manipulating the genome that will have pretty significant impacts on healthcare.

Today, the only way to do any of those tests is to do sequencing, and the reason for that is just because the existing instruments that are available—like PCR, where you can do a simplified workflow—can only detect a small number of targets. So, the only way to address some of these applications like early cancer screening is to have an instrument that can detect many targets. The only instrument that’s available today to do that is a sequencing instrument.

GEN Edge: How does Pleno’s tool compare with a sequencing instrument?

van Rooyen: A sequencing instrument is a very useful tool, but it’s more useful when you do not know what you’re looking for. It’s a discovery tool. COVID is a great example: when COVID started out, sequencing was used to discover the RNA sequence of the virus, but all the subsequent tests were done using PCR. The reason for that is because it’s a simple workflow, it’s low cost, it’s very easy to do—you don’t need tons of skilled labor.

In the same way, we are developing an instrument that’s a PCR-like instrument, meaning it’s the workflow of PCR to address these complicated ‘omic tests out there today. Without tests, if you know what the targets are that you’re looking for—and this is a very important point—you can use our instrument, you can multiplex the targets—be that proteins, methylation targets, DNA, or RNA. We can put them all together and have a PCR-like experience, simplifying workflow, to be able to do these tests. The technology that we’re developing is really key to all of this.

The instrument is a low-cost instrument, in the realm of PCR instruments. It’s not as expensive as sequencing instruments. The technology is based on a combination of biochemistry and telecommunication technology that we put together, where you can multiplex targets, cancel the interference between all these different targets, and do these important big tests in a much more simplified way. And it can be done today.

GEN Edge: How does Hypercoding draw upon telecom technology?

van Rooyen: Are you familiar with Qualcomm, which developed CDMA? [Code-Division Multiple Access, referring to any of several protocols used in second-generation (2G) and third-generation (3G) wireless communications] Think of what we’re doing as a CDMA system that gets implemented in biochemistry. Each user is assigned to each user—meaning a cell phone user or in our case, each target is assigned a code. Then you put them all together, and distinguish them from each other, because of the coding scheme.

Gavin Stone, Pleno’s Vice President of Product Development

Stone: If you think of PCR, it’s almost like using a two-way radio where if you and somebody else have a conversation, you take up a frequency channel. And if somebody else wants to have a conversation, you have switched to a different frequency to talk.

So, you can have a very small number of different people talking at the same time, whereas on a cellular network, where you have code multiplexing and you can have thousands of people all talking at the same time. Think of a stadium full of people watching a football match. And everybody’s able to be online, talk, do whatever they want. It’s because they’re using code multiplexing. For each of those people, the cell phone has got a different code that it’s using to communicate.

We do a very similar thing: Instead of PCR, where you have a color that determines what your target is, we have a code, so we can multiplex thousands of these codes together.

GEN Edge: What’s Pleno’s approach to signal processing, in terms of how fast or how precise if that’s quantified, as Pleno cites speed and precision among its advantages?

van Rooyen: Our whole workflow takes roughly the same time as a PCR workflow. Let’s say sample-to-answer is maybe a 2-hour timeframe. Again, if you compare that to PCR, it’s roughly in the same ballpark. But of course, PCR can only do a small number of targets. Ours can do thousands of targets.

For sequencing, that workflow is measured in days. Pleno is significantly more optimized and faster than a sequencing workflow. But the point here is really that it’s a PCR-like system. And workflow wise, we just extend the capabilities of a PCR-like system or a workflow into the realm of all these applications. That’s possible now.

Stone: The technology that we are implementing is not PCR. It’s Hypercoding. And the signal processing that we talked about, that’s where we figure out what all those codes are that are assigned to each of those targets on our instrument. So, it’s the processing of those codes—that’s what we refer to as signal processing.

GEN Edge: If Pleno’s technology had been in place, how much faster would it have been to figure out SARS-CoV-2?

Van Rooyen: Our goal, obviously, is over time, that people just buy one instrument, at least for PCR users, and that will be our instrument.  I can see us really making a big difference there.

Our tool is not for discovery. Sequencing is the right tool for discovery. And there are probably some applications that sequencing is better suited to. But for the majority of molecular assays with more than a number of targets, more than five or 10 targets, our technology can certainly replace—we are a new generation of technology for that space.

GEN Edge: How many targets per sample is Hypercoding capable of detecting?

van Rooyen: More than 10,000. Tens of thousands.

GEN Edge: And in terms of customers, would those primarily be pharmas, research labs, academic institutions?

van Rooyen: All of those, plus clinical labs, exactly.

GEN Edge: What sort of direction will further development of Hypercoding entail? It would seem that faster speed and more targets per sample are avenues, as are maybe even more samples per day?

van Rooyen: Yes, and all those avenues are open to us.

Stone: Even in the opposite direction, making a simplified instrument that’s fewer samples per day, fewer targets, but is something that can be deployed everywhere.

van Rooyen: Such as at point of care, it’s a very scalable technology that enables you to move on a lot of different vectors.

GEN Edge: In a point of care setting, how many targets would one even need and usually you’re looking?

van Rooyen: That is a good question. Let’s say, it’s early cancer screening, then it will be in the thousands.

Stone: You could think of like sepsis in hospital environments and all these kinds of multi-pathogen panels and things like that. So, hundreds to thousands to tens of thousands, potentially. But once the technology is available, people will use up whatever the kind of available space is, as with any other technology.

GEN Edge: We’ve seen a lot of activity in the sequencing realm as a lot of companies are looking to offer their own technologies to compete more with Illumina. We’ve seen Singular Genomics launch its G4 platform, and Ultima Genomics herald the arrival of the $100 genome through its UG 100 platform. How does Pleno’s platform compliment or supplant some of those technologies?

van Rooyen: Our platform and theirs are different tools, different applications. It’s in our benefit for people to discover tons of new targets, new applications. Once those are discovered, they can be deployed on our system. I don’t see them really as competition in any way.

Stone: It’s great that there’s all these other sequencing companies out there now. It just enables more and more people to go and discover more and more content that could be deployed in our platform.

GEN Edge: With COVID-19, what has to change in terms of capability, scalability, throughput? And how does Pleno lead the way on that?

Stone: At the moment, the detection is very narrow. You get a test and it’s you either have it or not, versus being able to know which variant you have. And there are two separate efforts. One is the individual testing. And then the population monitoring. And all of that could be combined into one kind of instrument workflow using our technology, where you can look at all the different variants and even go beyond COVID, where you can look at flu and cold and a whole host of other pathogens at the same time, so it becomes way more informative at a patient level rather than just, Do I have COVID or not?

GEN Edge: Pieter, you went from teaching electrical engineering as an academic to joining and nurturing startups–but also went from mobile health to genomics and now multiomics. What propelled you toward science and away from the mobile phone business?

van Rooyen: I’ve always been interested in genomics, and it’s actually very similar to signal processing coding. I mean, DNA is basically a code. So it’s sort of synergistic in a very basic way.

Stone: That’s where the word Hypercoding actually comes from. We’re applying an advanced coding scheme on top of another coding scheme.

GEN Edge: What happened between selling Edico Genome to Illumina and when you founded Pleno?

van Rooyen: I took some time off. I just inherently wanted to do something again. There are so many opportunities. I really think genomics specifically is like the new cell phones and the new Internet. It’s going to be the big technology in the future, so it’s exciting to be part of that. And having been a part of mobile phones and telecommunications, which changed the world, it’s really nice to be part of genomics as well. Pleno started on the premise that there’s just got to be a better way to detect targets if it’s known, as opposed to doing it in sequencing.

Another very important person in all of this, who joined us about August last year was Lorenzo Berti. He’s leading the R&D effort at Pleno. Together with him and some of the other people, we brainstormed and came up with what we have now. It’s groundbreaking technology and it was all developed in-house. We have about 30+ patents at the moment filed on the technology.

GEN Edge: Pleno says it employs 14 full-time people. By how much is that expected to increase over the coming year?

van Rooyen: Probably by Q1 next year, we’ll be 50 or 60 people. It will mainly be here in San Diego, of course. They will be both in engineering and on the science side.

GEN Edge: You mentioned most of that growing will be in San Diego. Will Pleno look to expand beyond there?

van Rooyen: COVID changed a lot of things. Software developers can probably be anywhere. However, lab people, science people working in the lab, will have to be here. So, we don’t have any intentions to split operations at this point, but we’ll see how things develop.

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