DeciBio Q&A

DeciBio’s Spatial Omics Q&A with Brian McKelligon of Akoya Biosciences

July 6, 2020
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Akoya Biosciences has gone public, will be joining the Russell 3000, penned agreements with Nikon, Zeiss, CrestOptics, Andor, and AstraZeneca, and discovered novel immunotherapy markers in collaboration with astronomists at Johns Hopkins University—and all of this happened in the first half of 2021. Akoya Biosciences has emerged as a key player in the spatial biology market, and I had the opportunity to speak with Brian McKelligon. You can find a transcript of our discussion below.

Brian McKelligon is the CEO of Akoya Biosciences and has guided the company through the acquisition of the Phenoptics portfolio from PerkinElmer and the development and launch of CODEX. Prior to joining Akoya in 2017, Brian served a variety of roles at Cellular Dynamics International, 10x Genomics, and Ion Torrent Systems (acquired by Life Technologies).

Brian, thank you for joining me today and congratulations on all the exciting developments coming out of Akoya so far this year, which have included not only going public, but also joining the Russell 3000 Index for their annual reconstitution. Maybe for people who are less familiar with the spatial biology field, could you provide a bit of background on the company, CODEX, and Phenoptics?

It’s a pretty unique story. The company was founded on the CODEX technology which came out of the lab of Dr. Garry Nolan at Stanford. Just a really prolific inventor in the life sciences space. That was the foundation of the company. I joined as the third employee in the middle of 2017, and we were working to get the CODEX system to market in 2019. Along the way, we had the opportunity, because of a relationship with our primary investor, to acquire a division of PerkinElmer. Now, that wasn’t originally PerkinElmer’s intent—they were looking to divest it—, but through the relationship with Telegraph Hill Partners, and through these discussions it became glaringly obvious that what CODEX could do and what Phenoptics was doing in spatial biology was highly synergistic. It made perfect sense for Akoya to raise a Series C and use those funds to buy the Phenoptics portfolio. That really became the foundation of the company that we are today. That acquisition gave us a product line that is very synergistic with CODEX. That’s a quick history of the company.

CODEX was obviously in a bit of a “stealth mode” getting it prepped for market back when the Phenoptics acquisition occurred. Now, most companies typically start by focusing on the basic and discovery settings with a platform, which then shifts over to the translational realm and down the line the clinic, but with this acquisition, Akoya pursued the translational field first before your discovery platform launched. What was the opportunity you saw jumping into the translational realm first with this established platform?

The timing—I say this a little backwards—the timing was almost secondary on which product came first. It’s kind of like a chicken and an egg. But for spatial biology, you’re exactly right, as we look back on the history of technologies in the life sciences, classically technologies start in discovery and work their way to become clinically relevant. What’s obvious and exciting about the spatial biology market is that there is immediate applicability today to have a meaningful impact from discovery through translational and clinical research. At the time of the acquisition of Phenoptics, it was the only system on the market that was providing an end-to-end spatial biology solution with instruments, reagents, and software. Phenoptics was, and still is, targeting the translational and clinical research market segment with a very clear objective of trying to solve some of the most pressing biomarker challenges in immuno-oncology. So, what we saw was a product that was purpose-built to solve a clinical and translational research need. That market opportunity went hand-in-hand with CODEX, which, like Phenoptics, provides an end-to-end solution for spatial biology, but for the discovery market. The result is a portfolio of products, CODEX and Phenoptics, purpose built to serve the very specific requirements of the discovery market and the translational and clinical research markets. On top of that, there was a team for Phenoptics already in place that understood this market. It had a couple hundred instruments already installed. It had a lead in both mindshare and placements because they were the first. When I joined Akoya and it was just CODEX, we asked ourselves who else was doing this, and at the time it was just PerkinElmer with Phenoptics. Now there are a lot more players. The ability to target both the discovery and translational settings simultaneously was really what became an exciting opportunity for us.

Definitely. As you mentioned, the field has really exploded over the past year and a half between proteomics and genomics. A lot of announcements coming from every which way and a lot of money being invested in this field. This has largely been built up around immuno-oncology, as you mentioned, and a new immuno-therapy biomarker has just been discovered through your work with Johns Hopkins University and AstroPath. It’s been an absolutely fascinating application of algorithms originally written for a completely different field of science, astronomy. How important has immuno-oncology been for these spatial biology platforms?

I/O has been central. Absolutely central to raising the value and the awareness of spatial biology. This is eerily similar to what we saw with the advancements of NGS, and the explosion of targeted therapeutics. They went hand-in-hand. They evolved in parallel. There was a mutual dependency, and I think the exact same thing is happening here with spatial biology. There has been some incredible work already with PDL1 as an IHC-based biomarker, and it sets the starting line for biomarker approaches. With the need to better understand the tumor micro-environment, spatial biology, and immuno-oncology, cancer and inflammatory response are getting inextricably tied.

Running with the translational theme, recently, I know I mentioned there were a number of exciting announcements from Akoya, the first part of the Strategic Clinical Research Program was launched with the introduction and rollout of Advanced Biopharma Solutions. This is geared towards the use of your platforms in drug development and later down the line in the clinic. This was coupled with a collaborative agreement with AstraZeneca. Immunotherapies, as you mentioned, have looked to protein markers in tissues, but have also expanded to include genomic markers, and targeted therapies have always had a strong use of genomics markers. Phenoptics is able to deliver these mid-plex proteomic images and analysis, how do you see this platform fitting into that evolving landscape?

I would reiterate two things before pulling back the aperture, pun intended, on what’s possible in the longer term. Spatial biology, Phenoptics, on the translational and clinical research side, is broadly deployed in I/O because that is inherently a question about space. Not just PDL1 alone, but PD1 and proximity to the CD8 cells—it’s a question of measuring the tumor immunogenicity as a likelihood of responding. Is your immune system poised to respond to an I/O therapy, a checkpoint inhibitor? It truly is a question of the spatial distribution of one’s immune cells within the tumor micro-environment. This is compared to targeted therapeutics where clinical decision-making is based on the mutational profile of a tumor. Again, and generally speaking, we have two different technologies with spatial and NGS each applicable to two different classes of cancer therapeutics, I/O and targeted therapies, respectively. So, longer term, with combinatorial therapeutics, whether it’s an I/O therapy with a targeted therapy or choosing between them, I think what you’ll see happen over time is spatial biology plus NGS may become the standard. One may require spatial approaches to understand immunogenicity and NGS to understand mutation types and mutational burden. In addition, ongoing monitoring post-treatment with liquid biopsy approaches, like Signatera, to measure response is also likely. If we pull back to that multi-year time frame, it’s not hard to postulate that this is where things end up.

That begins to address another question I had. We’ve seen other high-plex proteomics platforms target the clinic, thinking about something like a SomaLogic or an Olink, where it doesn’t have that spatial context, but for an application like immuno-oncology, it’s extremely important to get that spatial data and see how immune cells are penetrating a tumor and responding. You mentioned there being a space for NGS and genomics, liquid biopsy approaches, and the spatial proteomics approaches, do you find that, for spatial approaches, customers are more interested in proteins the closer you get to the clinic?

I think for the foreseeable future—even if you just look at the clinical trials biomarker data and the kinds of modalities being used, it’s either a protein-based detection system, with a lot of them being IHC, or NGS to look at mutational burden. In part, protein is also preferred because it is a stable analyte and a direct measurement of biological activity. Much of the gene expression work whether its RNASeq, single cell sequencing or spatial transcriptomics is within the early discovery markets. As you go farther and farther upstream to discovery, spatial transcriptomics, as an open-ended discovery platform, is incredibly powerful. So is high-plex immunofluorescence. They are really two different ways to approach the same question in a highly complementary manner. I think in the long-term, thinking back to the platforms you mentioned—SomaLogic and Olink—, there’s going to be a need to characterize these novel proteins, and that’s an opportunity for Akoya to address.

There’s been a ton of excitement around proteomics recently between companies we’ve already mentioned and others like Seer—people have definitely been mentioning this will be the “Decade of Proteomics” that’s coming after the Decade of Genomics. Getting back to these spatial genomics platforms, do you ultimately see these being complementary to a platform like CODEX? Would these platforms be getting used side-by-side?

I don’t think there is a binary choice to make between these two approaches. There are two paths forward, either taking tissue samples and running them on something like a CODEX and a Vizgen or taking a single sample and running it on a platform which can provide both genomics and proteomics data. We don’t know how it’s going to play out, but it’s not either-or. Ultimately, our customers have limits for capital equipment, so it’s going to be about who can deliver the best science.

CODEX can be complementary to Vizgen, Visium, Rebus, Resolve, or other spatial transcriptomics platforms that are coming out. For us, we think it’s important to explore both paths, supporting complementary data sets versus directly delivering multiomic data. That’s where we are. You might have seen the GenomeWeb webinar where we look at some of these datasets and algorithms are being developed for multiomic spatial analysis, and just like we saw with NGS and microarrays, the best bioinformatics and data analysis solutions don’t usually sit within the companies. You can’t bury your head in the sand, you have to really embrace and endorse data marriages on the informatics side to deliver multiomic answers across different platforms while you explore and invest in trying to come up with a multi-analyte approach on one sample. At least for us, we think that’s the wisest thing—to enable our customers to get actual value out of our data as quickly as possible.

As you just mentioned, there was a speaker series recently on multiomic analysis. Diving a bit deeper on this, how important do you think it will be to be able to build in things like single cell sequencing, spatial genomics data, and spatial proteomics data all together into a single type of analysis? How are you expecting your platforms to be used in this way in the future?

I’m going to answer this with respect to CODEX and we can hit the pause button on Phenoptics, because that will continue to advance farther and farther downstream to address the challenges today in I/O with a protein-based platform but recognizing we can do something like RNAscope on there today anyway. We have partnerships with big pharma where we are looking proteins with our Opal reagents and RNA with ACD’s RNAscope. When we look at CODEX, as we have already talked about, we’re trying to take a dual approach here. What we don’t have with CODEX, and I don’t mean this in a negative many, is a monolithic instrument. What’s really unique about CODEX is that it’s an in situ reagent delivery device. That’s what it does. It integrates with existing microscopes, whether they’re standard epifluorescence or next-gen microscopes, as we’ll cover on Zeiss, Nikon, and others. The power of CODEX is the ability to leverage that openness for new application development both internally and externally with partnerships. I think, for our approach to the spatial biology marker, we’re not trying to do it all and develop a fully encapsulated single-application box. We look at our opportunity in spatial biology with CODEX, and future versions of this system, as being able to catalyze and leverage expertise in this market with both our capital from the IPO for internal R&D expansion and through partnerships.

Maybe getting to Imaging Innovators, or the I2 Network, how important are programs like this for driving adoption for Akoya’s platforms, and what has been some of the most exciting work to come from other early adopters and Imaging Innovators?

Answering in reverse order here, since we just launched it it’s a little bit premature to proselytize on outcomes, but really at the core and the intent of it, is to expand the integration of CODEX with advanced microscopy solutions for application expansion. We don’t restrict ourselves to the typical internal product development methods. We have the ability to build a network of innovators who have high-resolution microscopy, confocal microscopy, 3D microscopy, other analyte types, and build a platform and an infrastructure in the customer’s environment that allows them to use our hardware for advancements. These can be microscopy advancements, they can be software, data analysis, across the entire workflow of CODEX, we have the ability to partner and innovate not just within our walls, but actively and proactively with our customers. That’s pretty unique, I think.

One thing you noted earlier was on the analysis side and how some of this multiomic analysis comes from a place where you have to be comfortable with it being developed in individual labs. Researchers are coming up with ways to marry these datasets and analyze them together. How important is developing that bioinformatics side going to be in the future? Obviously, this is something which has lagged behind the abilities on the upper end of plex. How important do you think this will be looking forward?

I think it’s the centerpiece of the whole market, ultimately. Imagine us having a whole genome sequencer and having very limited bioinformatics capabilities. This is one of those instances where platforms have advanced very quickly, and now we’re going to see an explosion of incredibly novel approaches to analyzing the data. That’s going to come from academics, industry players like Indica and VisioPharm, from us—what we all have to figure out how to do is how do you build a software framework that allows inventions to plug in. That’s part of our vision with Proxima, which is only in its early stages now, it’s not just the collaboration and sharing of data, and it’s not just our analysis capabilities and making those cloud-enabled over time but building an environment that allows for third parties to plug into that so we can achieve one plus one equals three.

Even looking outside of our immediate data types and to a very close neighbor and seeing what groups like PathAI are doing with H&E images. That’s an incredible example of what’s possible. I think we’re beginning to scratch the surface. I think we’ll have powerful solutions that come from internal and external sources in short order. There’s been a lot of investment in it, including by us.

Definitely, and, obviously, you have the AstroPath program ongoing which is generating some super exciting insights. To begin to wrap us up, and getting back to something you mentioned already, the co-marketing agreement with Zeiss was announced last month and just this week partnerships with Nikon, CrestOptics, and Andor were also announced. Specifically looking to something like the I2 Network, how are these partnerships going to help drive adoption and how are they going to be helping achieve this goal of expanding the integration of CODEX?

So, there are a couple of things. Having the direct relationships allows us to be ahead of the curve on insuring robust integration and a streamlined user experience. The workflows are linked, synced, and we can work together to make them faster and more powerful. That’s the obvious technical integration. Our ability to co-promote together is more than just about creating leads and that 1+1 is 3 when it comes to the market, but also allows us to formally endorse each other, which I think is meaningful. We believe in each other as partners when it comes to delivering real value to customers. That collaboration gives our customers the confidence that the integration of these systems over time is not just stable but will continue to advance. That’s today, and we already talked about tomorrow as we look at application expansion.

To add one more thing to really hammer it home, microscopy is really advancing. There are a lot of incredible things coming out of a lot of these departments, and what CODEX, being a fluidics integration system, allows us to do is not have to lock down our optics. We don’t have to lock down to a single microscope, we don’t have to lock down our assays, and if we want to launch a new assay it’s just a new set of reagents. We are able to decouple microscopy from the assays and this system, and not have to go through these long development cycles where you have a limited system, and it becomes an incredibly powerful use of capital.

Well, we’ve seen this and it’s obvious—this approach works. We’ve seen other instruments using existing install bases to smooth that transition for a new technology or a novel application of a technology whether that’s in the spatial field or, looking to Seer, with a completely novel use of a technology like mass spec. It’s a path that works and no doubt will be successful for CODEX as well. To wrap us up, any other final thoughts on what we’ve discussed or any other exciting pieces to look for from Akoya?

I think we’re going to continue to advance and be great at the workflows and products we have today. We’re going to look for that expansion and new capabilities on the discovery side. Continue to advance and improve the power and clinical utility of the Phenoptics portfolio. I would just say, if you look at how this market has evolved over the past couple of years, we’re just thankful to be a part of this and hopefully be seen as leaders in this market. We’re all just beginning. Not just us, but all of the companies in this market. The amount of investment that’s gone into spatial biology is a benefit to the entire market and ultimately for patient care. I think it’s an exciting time as you look at how far NGS has come, and then you look at the investments in proteomics as a new, powerful discovery engine, and then spatial biology—it really does feel like an incredibly powerful market.

Authors
Max Jorgensen
Associate & MarketBook Manager
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