Welcome to the DeciBiome. This is our space for speaking to life sciences leaders and tracking the latest industry developments across precision medicine.

I'm pleased to be joined by Selena Larkin, the Chief Commercial Officer (CCO) of RareCyte. We have an exciting conversation planned on RareCyte’s commercial outlook and product roadmaps across two emergent industries in precision medicine: Spatial biology and liquid biopsy (LBx).

So before we dive in, let me say it's a pleasure to have you on here Selena. We really want to get to know a little bit more about yourself. What we've been able to learn so far is that you have a very extensive professional history in life sciences business development and commercial strategy with a growing expertise in research tools and diagnostics. This started with your PhD in Protein Chemistry from the University of Melbourne all the way to your most recent strategic commercial programs at Waters Corporation. Thinking back throughout your life, what are some of the formative experiences that prepared you for your current role and have shaped the philosophies that you bring to your role as the CCO of RareCyte.

Well, thank you very much for the opportunity. This is wonderful. I've really had a privilege throughout my career to be able to focus on the development and commercialization of enabling technologies to the life sciences space and it's exciting for me.

I really have a passion about what I do, and that passion is very much aligned with the mission of RareCyte, which is to bring enabling tools, technologies, and services to precision medicine and to biopharmaceutical research. It is really exciting the areas in which we’re working rare cell analysis and spatial biology are both very exciting growth areas to be in. So, between that and the first-class team, I really feel very privileged being able to bring my experience to work every day.

So, some formative things. Probably the most important things I've taken from my career are to listen to the customer. To really understand their needs and that they will help you as an organization develop your tools and your applications.

The second one is that relationships are all important. Between the relationships that the RareCyte team brings and that I bring from my background, we find that we're opening a lot of doors. We're getting good conversations and we're able to really kickstart those conversations to help get technology into people's lives.

That's great. How did you end up getting into this line of work in the research tools and services field? How did that transition happen throughout your career?

I started out as a capital equipment salesperson working primarily for large multinational companies. I then took a role at a smaller venture funded company where our technology was very new, very young, and we needed to break into the space. So, they allowed people an opportunity to try before they buy, and we really built an entire franchise around our contract research offering. We found over time that people liked working with us in both ways. Some people wanted an instrument on their own bench, and they wanted to do the work inside. A lot of people in pharmaceutical companies particularly have a model of outsourcing, so what started as a way of getting our technology into the marketplace ended up being a very fulfilling and satisfying business model that I will say I have had the opportunity to replicate a number of times over the years.

Fascinating, that seems to mimic slightly the work that you're doing at RareCyte where you have platform offerings as well as service offerings. It seems to create an ecosystem of collaboration for your customers, so that's great to hear.

It's true. By having that level of customer intimacy and working with them on programs, it helps us understand their challenges, their needs, whether it be in regard to workflow or if there are opportunities for assays or products that they would find useful and interesting. The fact that they find a particular analysis valuable means that others very likely do also, and that really helps drive our product roadmap with which assays to develop and commercialize as kits, for example.

You potentially touched on some of the things I wanted to ask, but before we get into spatial biology, RareCyte is a really interesting and dynamic company. As you mentioned, you have the Precision Biology Services for clinical assay development and trial support through your CLIA-lab network and then you also have distinct platforms in CyteFinder II for liquid biopsy and Orion, now, for spatial biology.

It'd be interesting to hear from you how you would describe RareCyte’s business model and how these distinct parts coalesce into a targeted strategy.

We really cover the user-spectrum with our tools, from discovery through translation, validation, and implementation in pharmaceutical and clinical labs as LDTs (laboratory developed tests), leading to companion diagnostics (CDx).

The high-plex Orion system is primarily being used by our customers for validation of spatial biomarkers and for comprehensive phenotyping and profiling spatial analysis of the tissue microenvironment (TME). CyteFinder, as you mentioned, has been established for studies using targeted panels with lower plex, but very high throughput (HT). We have the CyteFinder II HT which is a high capacity, walk-away system. You can load it up with 80 slides, go away and have it run through all of them regardless of whether it's a liquid biopsy assay looking for rare cells or for tissue analysis.

It’s a nice portfolio and our business model is to make those technologies available to people wherever and however they need through sale of instruments and provision of contract services. RareCyte’s Precision Biology Services team is led by Leighton Howells and offers end-to-end services from custom assay development to clinical trial testing for researchers, translational scientists, and drug development and diagnostics organizations around the world.

So, we'll go ahead and get into spatial biology. I wanted to take a second to just briefly define what we mean by this. I know in our world of precision medicine we throw around a lot of terms that most people don't understand. Spatial biology we're defining as the analysis of target analytes in tissue in a spatial context. This is mainly around protein and transcriptomic information such as RNA, but it can be other analytes too.

So now we've got that out of the way. The exciting news at hand is that in 2020, you announced the launch of your Orion, Spatial Biology, platform. As you mentioned, multi-plex with 21 fluorescent channels, strong resolution, in rapid turnaround time for spatial omics imaging analysis. Recently, you raised an additional $24 million USD in funding led by Arboretum Ventures that's primarily aimed at advancing this platform.

It'd be great to hear what the inspiration was for Orion and why the decision was made to pursue spatial biology? Moreso, with this new funding and a lot of energy going behind this platform what are the initiatives that will be forming around Orion?

A bit about the philosophy and the inspiration - we at RareCyte do pride ourselves on being a precision analytical company where our focus is primarily on multiplexed immunofluorescence imaging. We want to make sure that we deliver data that is robust and can be trusted in critical studies such as biomarker validation, clinical patient stratification and clinical implementation.

The inspiration here was that there were platforms on the market, like CyteFinder for example, that looked at targeted numbers of biomarkers and where it was possible to take a test into the clinic or into a pharmaceutical drug discovery format, but that developing these tests requires doing higher plex analysis of the very complex tissue microenvironment. A platform was needed to investigate not only the presence of markers, but also the quantitation, subcellular location, and the distance between different cell types – all of which is very important and requires very reliable, reproducible profiling.

Customers came to us and said, “we love CyteFinder” and many of our customers had implemented cyclic immunofluorescent processes where they take a CyteFinder and use up to four markers, usually with a nuclear stain, they'll stain the slide, scan it, then they either strip or quench and do another layer, and another layer, and then combine those images.

As far as being robust enough for biomarker validation, the cycling approach is very, very challenging for a lot of reasons, not to mention kind of slow and laborious. So customers came to us and said: “Well, you guys have done a really good job with the CyteFinder platform. Can you develop something that's higher plex so that if we do have a scientific hypothesis, we can look at enough markers at once to be able to answer that question - and ideally be able to do same-slide analysis using standard histopathology like an H&E stain. We want to measure the biomarker molecular information in a quantitative manner over a broad dynamic range with high sensitivity, high precision, etc. and look at H&E too.”

The same slide analysis makes sense because it allows users to correlate the intuitive information that a pathologist learns to derive from H&E and bring that to bear upon the very same slide and tissue from which they're getting spatial biomarker measurement. It has proven very valuable..

What initiatives are coming up with this funding and generally in the future?

So, as you noted, primarily focused on Orion - building out the commercial team, building out R&D capabilities to support product development, and then, of course, the normal sort of corporate and administrative investments as well.

From an R&D side, main areas that we're focused on are, with an install base of instruments around the world now, taking our learnings from our customers, our current users, and building the menu of validated panels and biomarkers that people can use without having to build it themselves. Also to make the technology amenable to anyone across the spectrum through really cost-effective and easy to use kits, so that people can label their own antibodies for maximum flexibility.

Then, the other side of it really is continuous development and improvement of pipeline tools for interpretation of this very valuable, complex data.

So, there's a lot going on. It sounds like you already have platforms that are being placed internationally for Orion?

Yes, we do. We are continuing to grow that install base and it's exciting because we are at a point now where customers are generating some superb studies, really useful data and they're going out and talking about it with their colleagues and at conferences.

I think 2023 will be a very important year for Orion and building on all the work and the investment that not only we have put in, but that our customers have put in as well.

A lot of what I'm hearing potentially is that this might be starting as more of a research discovery platform with targeted panels coming along that might be validated and pushed more towards clinical applications. Is there any desire for moving into translational and clinical spaces as well?

At RareCyte as a standard, we always develop our platforms with the eye to the clinic in the end, and that's what drives our rigor. It keeps our compass pointing towards rigor, high data quality and fidelity, and reproducibility. We control our own manufacturing in our ISO 13485 audited facility and do extensive testing, of all our instruments, kits and reagents for reproducibility and stability. We believe it is vital that our customers  feel confident utilizing all our products.

With these research reagent panels, validating spatial biomarkers still is a very complex thing.  We have focused on delivering flexibility for researchers to use our reagents to look at sets of markers that have perhaps not been studied together in groups before in such a rigorous way. It's very exciting to be enabling customers across the board from academic researchers, translational researchers, and biopharmaceutical companies.

That was going to be my next question: Is this getting into academic medical centers, research institutes or also large and small / medium biopharma? It seems like it's a mix.

It is a mix, all the above, which is interesting. It provides a good challenge, not only on the sample preparation and reagent side of things, but also on the data interpretation side because different clients have different needs.

We do offer both Orion and CyteFinder services through our pharma services CLIA-certified labs. We're working on a lot of programs at any given moment in time and we're getting the experience of what people need when it comes to interpretation. We're learning every day, we're building our team, growing our biology team and our software team in support of that.

To answer your question, instruments, and service programs across the board through academic and pharma research which makes for a very exciting set of opportunities.

Are there any partnerships or research collaborations that are exciting and ongoing? Sometimes you'll have an academic researcher that's specialized in a certain space that's doing great work or a biopharma company that's taking a certain interest in the platform’s capabilities.

We have had the opportunity to present or publish a number of our programs that are established on the CyteFinder platform. You probably are aware that the Norris Comprehensive Cancer Center at University of Southern California and the Mayo Clinic have been running multi-year circulating tumor cell studies using our platform as have other institutions worldwide. Other rare cell analysis includes studies of pleural effusions published by Stanford University.

We recently were awarded some very nice awards. One is from the Gastrointestinal Research Foundation for looking at circulating tumor cells in gastric cancer  We were also selected for the Wellcome Leap Foundation-In Utero Program looking at rare fetal cells in maternal blood to understand placental development, with the end goal of reducing the global stillbirth rate by 50%. We're doing some very exciting stuff, but that's all CyteFinder.

As far as Orion and the partnerships we have there, between the service work that we're doing with our clients, and our growing base of instrument customers, we are very excited that they will be able to publish and speak about some of that over the next year. We’re always working, not only with other tool and solution providers, but also with our clients.

That’s all very great research and collaborations. Frankly, that’s what’s special about this work in precision medicine. There’s always a cause you’re furthering. There’s always a field of biological or clinical knowledge that’s being expanded, and for a good purpose like curing disease or having more insight into the disease. That’s very exciting to hear all around.

Then, in spatial biology, we recently released our market report for 2022 where we did an in-depth analysis of the industry. There are some major players in the space. Of course, we know Akoya Biosciences, NanoString Technologies, UltiVue, 10x Genomics which have strong market shares, market presence and it’d be interesting to understand why you think now was the right time to enter spatial biology? Was it a complement to internal services and expertise? Frankly in this field that is pretty competitive.

It is pretty competitive and there certainly are platforms that have been available for a number of years, but that said, there are still some really significant gaps.

The real motivation for developing Orion was based upon customer need. Going out and talking with the RareCyte customer install base it became sort of a groundswell of agreement that, in order to further the whole spatial biology space, a high precision, high fidelity data delivery platform was necessary— one of the real challenges with existing platforms.

First, let's step back a little and talk about actual biomarkers. At RareCyte, we do focus primarily on proteins versus genomic markers and proteins represent the vast majority of drug targets, with the market growth of antibody drug conjugates (ADCs) and in drug development, coupled with an unmet need in immunotherapy we do see a huge opportunity in that space. We are focused on high plex with fast turnaround compared with the other platforms that look at proteins. Our customers needed to be able to run enough samples fast enough to get through enough patient samples to drive statistical significance for what they're looking at. The more markers that you add to a panel of analysis, the more data points you have, the more noise you have, and the more patients you need in order to drive statistical significance. So, it was in response to needs that we developed Orion.

An example of where Orion has been used in translational study for biomarker validation is a recent study out of Harvard University where they sought out spatial biomarkers using a clinical cohort for which they have progression-free survival (PFS) outcome data available for every patient. They looked at Orion as a platform for being able to identify spatial biomarkers that would separate groups of patients and be very highly correlated with their outcome.

They were able to find hundreds of prognostic spatial biomarkers with Orion by using multiplex staining of seventeen markers in a single cocktail and scanning all the channels at once at a rate of about 70 minutes per square centimeter. By taking permutations and combinations of the plexed markers at cellular resolution over the entire slide with same-slide H&E data, they obtained a really detailed understanding of the cellular microenvironment and found spatial biomarkers that clearly separated the patients by way of clinical outcome.

It's already being used in translational applications — some patient stratification, some prognosis. That's great stuff and I'm sure the people who are listening in and researchers are taking notes. They're getting ready.

Now we'll move on to liquid biopsy, which is another big part of RareCyte’s business. To give a little bit of background on liquid biopsy — I was asked a question recently about what that means because it is an abstract term to be thrown around. To define liquid biopsy, it's non-solid tissue-based biopsies. This is typically when you take out a piece of tissue, scan it, diagnose it, run tests on it. This is growingly used in blood as the sample type, as opposed to tissue, and for cancer diagnosis, treatment, selection, prognosis, and monitoring. They look for molecular analytes — usually cell-free circulating tumor DNA (cf/ctDNA) that regularly sheds from tumors throughout their life cycle. So that's the state of it. Essentially, you take a blood sample, you send it to a lab, they process that, they sequence it, and then you can see if there are common oncogenic or tumor suppressor gene (cancer causing) mutations in the patient sample that are popping up.

RareCyte on the other hand is very differentiated. It's a unique liquid biopsy company in that your analytes are circulating tumor cells and rare cells as opposed to only sub-cellular analytes. It's also a platform-based approach with CyteFinder where you have to have access to the instrumentation to run the test and it's not necessarily just through a CLIA-lab service where you send in your samples or potentially run them on different types of equipment that are commonplace such as Illumina sequencers.

With that background context, what motivates your commitment to circulating tumor cell-based liquid biopsy, since it's so different from what the rest of the industry is currently doing?

Frankly, our motivation is the continued interest - and the growing interest - that we're seeing in the analysis of rare circulating cells.  This is across research, pharma, drug discovery and clinical diagnostic development.

To restate your description of liquid biopsy. I think most people are very familiar with the idea of measuring circulating proteins in plasma such as CEA (carcinoembryonic antigen), or PSA (prostate-specific antigen), as indicators of cancer. Also, measuring circulating tumor DNA, which are fragments of DNA that are spilled into the plasma when cancer cells are killed.

What we do is a bit of a different approach. Rather than looking at the plasma — and we do, by the way, prepare very nice clean plasma with our sample prep methodologies and kits — what we do is look at all the nucleated cells, with circulating tumor cells being part of that. It's important to remember that CTCs really inform on the cancer cells that are resistant to a first line therapeutic. If you have a CTC in your system, it's a viable cell that has survived therapy and has metastatic potential to set up shop somewhere else in the body.

Finding and counting CTCs is important, but what is also important is the ability to isolate these cells. Using CyteFinder multiplexed imaging you can visualize what potential drug targets are present on cells. You can then pick the CTCs, to isolate them for genomic analysis with access to the entire genome. We're taking a truly multi-omic approach and this is really important, especially for our pharma drug discovery and development customers since it allows them to develop alternative therapeutic approaches.  

We're seeing a huge amount of interest there and it is reflected in the growth of our pharma services business, for sure, and also in the number of instruments that we've sold. Whether it be for circulating tumor cells, circulating fetal cells, or other rare populations, rare cell analysis is seeing a significant surge in interest.

How would you go about defining the different levels of information you can get from a cell as opposed to these single analyte approaches or molecular analytes, in being able to recover that single cell intact essentially. What's the added value there?

You can do truly multi-omic analysis, which I think people are very interested in. You get cellular information, you get protein information, you get drug target status information as well your access to the entire genome of that resistant cell, which is very different from getting fragmented DNA, which can be confounded depending on the health status of the patient. We know that, immediately following resection, patients will have significant amounts of circulating cell-free DNA in their system because of the trauma of the surgery, so it can be very confounding when looking for circulating tumor DNA. Whereas here, we're looking at a very clean isolation and true single cell analysis - which has become a Holy Grail component of clinical research recently.

To clarify, it sounds like in addition to on-platform assays that you've developed for CyteFinder that you perform with the recovered cells, you can do downstream testing such as sequencing, for example? What are people tending to do with the cells they recover?

We've developed techniques ourselves and our customers have developed their own methodologies to do DNA sequencing, usually targeted sequencing, although it is possible to do whole genome sequencing (WGS) if you wish, and people also do RNA-seq analysis on those cells. It opens a huge amount of additional information.

You had also touched on the question about centralized versus decentralized testing. How do people really get access to doing this?

We at RareCyte do offer services in our own CLIA-lab, but we do also work with a number of global CRO’s so that we have customers around the globe doing local blood collection, local sample prep, and even doing analysis on the CyteFinder systems that they've bought and set up in their own labs. There are central labs in the Americas, in Europe, and collection labs in countries around the world that are doing this analysis. Then, many customers decide that they would like to buy their own system and run it too.

If you're doing CTC analysis with our unattended CyteFinder HT (high throughput) system, you can load up 80 samples, it's all barcode driven, and we have machine learning algorithms on board that identify, enumerate the cells, and tell you exactly where they are so that if you want to go back and pick them off the slide, you can do that. Running at 10 minutes or so per slide for 80 slides unattended means that there are labs around the world that customers can access making a very good business out of doing this work on our platforms.

Thank you for bringing that up. The more I thought about that topic — this is something that comes up a lot in our talks about liquid biopsy — this concept of centralization versus decentralized testing. To give people background, centralization is essentially if you take a sample and send it into a lab that represents a company or an institute that can process high numbers of samples. Decentralized, on the other hand, is when I can do kits on my own internal equipment at my company or my lab specifically.

It's essentially decentralized with your platform, but I don't think there is a clear answer. It could be decentralized theoretically if you adopt the platform in-house or if you choose to use it through service offerings more so centralized. Have you seen a skew towards one or the other? Is it more centralized?

It depends a lot on the background expertise and the infrastructure that a customer has and their philosophy around how they generate their analytical data. For example, a lot of pharmaceutical companies prefer to outsource rather than having the instrumentation in-house whilst others do prefer to do the work on their own.

I think what we've seen is that people will start out using either our RareCyte Pharma Services or they'll work with a Contract Research Organization with which they already have an established relationship. There's a number of them listed on our website, such as CellCarta, NeoGenomics, and ICON, that provide specialized testing as well as broader clinical trial management. Quite often our customers start working with us in that way.

We've had several examples where the pharma company will then buy one or multiple CyteFinders of their own. They'll use those systems to develop new assays to deploy to their CRO partners, or to run their own samples in-house. It depends very much on the philosophy of the company, but we've seen it work both ways, and it is our mission to make our technology available to people in ways the market needs so we continue to support both sides of this model.

It's great that you brought that up because that dynamic of outsourcing for biopharma companies, either due to limited personnel or budget needs, or just exploring and piloting new technologies, is what we tend to see across different specialized platform technologies. People want to try it out, get a sense for the data it's producing what the actionable outputs are and then once they're committed, they bring it in. It's great that you have both options.

We're getting close to the end here. Another big topic we want to mention if you'd like are your Precision Biology Services. There was an exciting mention in a press release that your sales and 2021 increased 100% YoY (year over year), so clearly you're doing something right. Are there any interesting developments around your Precision Biology Services that might have really kicked off that growth or are helping push you in that direction?

We beefed up our capability and our bandwidth during the pandemic to support our customers and that has served both them and us incredibly well. We've been able to continue to grow upon that influx of service business since then.

That also helped drive our instrument business because it's got more people exposed to the technology. Now that they're back in their labs and that able to focus on new studies and new technologies, we're seeing people that were Pharma Services customers bringing RareCyte instruments into their institutions.

That is a good point. You bring up that there was a COVID effect in biotech and biopharma where most players got a lot of business during the pandemic and it was a great time, and now we’re in this new market environment that's much more uncertain. Are you taking any actions or preparing for certain market conditions, potential changes in demand or do you feel confident about steering ahead in 2023?

I believe we're in a different situation at RareCyte versus many of the companies that experienced a tailwind during the pandemic. I think it’s because RareCyte serves such a high-growth space that we got that boost from outsourcing and now we're continuing to benefit from the momentum.

Spatial Biology truly is a hot field - indeed it is the topic for the upcoming ALDA Spring Senior Executive Conference – and with such great response to our portfolio we are looking forward to an exciting year in 2023

Our Pharma Services business helped us to learn from our customers and to get our foot in the door for conversations about Orion. That has proven immensely helpful for a product launched in the midst of a pandemic where customer visits were not feasible. Being able to generate data and get customers up and running on a new platform through a bifurcated business model definitely has been a benefit. We've built our team to be really responsive to our customers, and we intend to continue to be so.

That's all great here. I'm happy that it's going well, and you foresee a strong future as well. Any last points you'd like to bring up any, any future developments, anything that maybe we missed that you wanted to cover in our call?

The main thing is for your audience to know that we at RareCyte are focused specifically on these areas of spatial biology and rare cell analysis, and we have not only the motivation but the knowhow and resources to be very responsive to customer needs.

If there's anyone listening or reading who has an idea in mind for how they think that we could work together, I’d encourage them to please reach out. We love running programs with our customers because it helps build our understanding of different workflows and the kinds of studies and analytes investigators are interested in. That helps us develop our assays and portfolio serve our industry better. Please feel free to reach out to us.

It's been a pleasure meeting with you. All of your work sounds exciting. It's a great contribution to precision medicine and we’re very excited to see what lies ahead for RareCyte.

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