10x Genomics, Inc. (TXG) Earnings Call Transcript & Summary

Hi, everyone. Thank you for joining us today for the webinar. My name is Mio Tonouchi, I am the Director of Marketing for the Asia Pacific region, and I'll be hosting today's session. And we are really excited for today because we had an announcement of the new solutions and also the products to come this year and next. And today, I invited a few product marketing manager from the headquarters to go over some of the details. Next slide, please. Cool. So we have 2 sessions. The first one, we're going to spend the first 20 to 25 minutes talking about the single cell solutions. As you can see, there are 5 product updates that we write down. And Dina Finan, who is a product manager for the single cell, Zuley Peralta who is the product manager for sample as well as Samantha Shelton for the high-throughput single cell, they will be speaking on these products. And using the second half of the webinar, I will cover on the spatial solutions as well. So if you have any questions during the session, please feel free to submit through the Q&A chat box so that we can address that at the end. So with that, I'll hand it over to you, Sam, so that you can get started.

Thanks, Mio. Thanks, everyone, for joining. We're really excited to be here today to talk about some of our new solutions. So at 10x Genomics, we really see ourselves as advancing biology and creating new tools for researchers to advance biology across our 3 complementary product platforms. So the first of these is our Chromium single cell platform, which has enabled tons of discoveries across many different research areas, including oncology, immunology and neuroscience. And has allowed researchers to do things like discover new cell types, identify new gene signatures and really deeply characterize the heterogeneity of many different sample types. Next, we have our Visium Spatial platform, which will be highlighted later by Courtney and Jyoti, which greatly enables researchers to profile the heterogeneity of their tissues while also maintaining the morphological context as well. And Courtney and Jyoti are going to talk about some of the exciting new developments that we have coming there. And lastly, we are also building our third product platform, our Xenium In Situ platform, which will be a more targeted approach compared to our Chromium single cell and Visium Spatial platforms, which are better for early-stage discovery. But we're really excited about that platform as well. And I believe Courtney and Jyoti will talk about that a little bit in addition, and that will be released later this year. And so with that, I do want to start by highlighting our Chromium single cell platform and just how far we've come even through 2021. So we released our first single cell gene expression product just actually only about 5 years ago. But we've really come a long way since then releasing tons of new products that have enabled a wide array of discoveries including our immune profiling solution, our targeted gene expression product, our Multiome ATAC+Gene Expression product to profile open chromatin as well as gene expression data from the same cell. And more recently, we released our newest instrument, which is the Chromium X series of instruments, which is compatible with our single cell high-throughput assays. And we're really excited -- we're always really excited to talk about these products. We're very proud to show that it's not just us that thinks that these products are exciting and innovative. Our products have made it to the Scientists' Top 10 Innovations of the Year list of the past 5 years. And this most recent year, our -- the products which made it to this list was our Chromium X product, which allows researchers to scale up the single cell experiments and achieve cost as low as $0.02 per cell. And we can also see that researchers share the enthusiasm of these products as well, just looking at the number of publications. This slide is -- constantly needs to be updated. And so I think is usually out of date. I think, yes, as you can see, we actually have 3,400 publications now. And this just goes to show how single cell research is being used more and more frequently to fuel discoveries across the life sciences. And it's been used in a wide array of different research areas and topics, including discovering new cell types in cancer, understanding the early stages of embryo -- of organogenesis and looking at neuro pathogenesis as well. So really just from every research area, I think has been touched by the power of single cell sequencing. So as I mentioned, the Chromium X is our latest instrument, and we're really excited about this instrument launch for a number of reasons. The first is the degree of throughput flexibility. So the Chromium X is the instrument with the highest degree of throughput flexibility on the market. What we mean by that is that it has the ability to go from very low throughput samples, very low throughput cell loads for those pilot and early-stage experiments, all the way to the highest throughput experiments very easily depending on what your research needs are. In addition to being -- in addition to having this range of throughput flexibility, it also provides a one-stop shop for all single cell assays. So as I mentioned earlier, we have had -- we released a number of single cell assays over the past few years. And the Chromium X can run all of our on-market products currently. And this includes products for single cell gene expression, single-cell immune profiling as well as for Single Cell ATAC and mostly on the ATAC+GENE expression. So it really provides a one-stop shop for any researcher who's interested in looking at biology at the single cell level. Compatibility with our high throughput products makes it ideal for researchers who want to achieve economies of scale for those larger scale experiments. So for experiments where you might need hundreds of thousands of cells, for example, for cell [ Atlasing ] or deep tissue profiling you can -- those experiments are brought much more within reach with our high throughput assays. And lastly, our instrument is extremely easy to use. It's an intuitive user interface, more advanced sensors, which allows for better support and troubleshooting. As I mentioned, the Chromium X is compatible with our complete single -- a complete suite of single-cell assays which allows for the most comprehensive selection of assay types, which allows for deeper profiling of your sample. So it's possible -- so again, with using our Chromium X, it's possible to look at chromatin accessibility perform CRISPR screens, look at single cell gene expression, sequence T and B cell receptor sequences and profile cell surface protein markers, all from the same single cell, using our complete suite of single cell assays. So really excited about the instrument's ability to handle a diverse array of assay types. Additionally, as I mentioned, the degree of -- the range of throughput flexibility allows for researchers to perform experiments in any stage of studies that they're at. So for the small-scale experiments where you maybe are just piloting out a new sample type and you want to see if the data that you get is interesting. For that, the Chromium X is compatible with our single-cell gene expression [ LT ] product. For those [Technical Difficulty] experiments where you want to [Technical Difficulty] cell types and profile your sample a bit deeper. Our standard single-cell gene expression solution provides throughput in the range of 500 to 10,000 cells per channel. And lastly, for those large-scale experiments where you really need to profile your sample very deeply, our single-cell gene expression HT assay allows for profiling cells -- samples from 2,000 to 20,000 cells per channel. And this ability to run the HT assays allows researchers to achieve much lower total project costs for these -- for their projects that are really, really high scale. So in this particular example, we performed a high-throughput drug screen using our single cell gene expression HT and our CellPlex pipeline. And what we did here was we took a 96-well plate, which you can see here. We then loaded the 96-well plate with the non-small cell lung cancer cell lines, 2 different cell lines. And then we treated both of these different cell lines with a variety of drug -- with a variety of different drugs, at different time points. And then we pull -- we labeled these different cells -- we labeled these different samples with our CellPlex products. And from there, we were able to pull all of these samples together, knowing that we could de-multiplex them on the [ biogenetics ] end using our CellPlex product. We pulled all these samples together and ran them across 16 lanes of our high-throughput chip, in a single high-throughput experiment run. And this generated 48 simultaneous conditions, which we were able to visualize in the 3D map here. You can see that there's a ton of data to dig into here. But just as an example, you can see how the [ cabozantinib-treated ] cells in particular, for these cells in blue here have a very strong change in phenotype compared to the erlotinib/osimertinib treated cell line. And so this whole project would have been -- could be quite costly using our standard kits and reagents as well as not doing targeted sequencing but doing whole transcriptive sequencing. But when we combine our high-throughput kits and reagents along with our CellPlex product line and our targeted gene expression assay, which helps us cut down on sequencing costs. You can see that we're able to reduce the total cost of the project by about 70%, which allows us to really think about scaling up experiments and open the doors to new types of experiments that can be performed. This is just another way of looking at the total drop in project costs that's achieved with our high-throughput assays. And so here, if you look at the overall cost per cell, using our standard assay starting in 2016, the cost per cell was about $0.15 per cell. So you can see how over time and the introduction of these new products we've launched, including CellPlex and HT, cost per cell has dropped dramatically for those high throughput experiments. Okay. So that covered our most recent innovation of the Chromium X and our high throughput assays. And next, we're going to talk a little bit about some of the new products that we have coming up in 2022. So the first of these is our 5 prime Feature Barcoding on our Chromium Connect. And our Chromium Connect is our automated single cell platform, which allows you to basically load cells, load the reagents and then run your assay with walkaway convenience. So our 5 prime single cell immune profiling assay is currently available in the Chromium Connect, but we're now releasing this with compatibility for our 5 prime Feature Barcoding assay as well. This allow researchers to perform single cell immune profiling plus gene expression with full length paired V(D)J transcripts that will also be compatible with cell surface proteins, and we expect it to be launched in the middle of this year. Next, we have our 5 prime CRISPR assay that is also being released early in the year. And our 5 prime CRISPR assay is really cool because in addition to being able to detect gene expression as well as guide RNAs at the single cell level, we're also able to detect multi-omic readouts in addition. So here, we're able to attack cell surface protein expression as well as the expression of TCRs and PCRs, all through the same single sample using this assay. Additionally, the other nice thing about the 5 prime CRISPR assay is that it will be off-the-shelf compatible with most existing Cas9 libraries. So it won't require additional modification or optimization or tweaking of your guys in order to get it to work. Most Cas9 libraries will just work off the shelf. This makes it very convenient to fit into your existing CRISPR screening workflows. Finally, I'm going to cover a little bit about BEAM before I turn it over to Dina. So BEAM is our antigen profiling product that is built off our single-cell immune profiling solution and is expected later this year. And this will be enabled in kind of two flavors. So we'll have BEAM-Ab, which will be our high throughput antibody discovery platform. as well as BEAM-T, which will be able to look at antigen-specific TCR receptor sequences and both will be launching later this year. And it allows for comprehensive surveillance of the adaptive immune system at scale. To show what kind of data this can generate, this is an example where we use BEAM to [ tag ] COVID-19 antigens with 10x barcode. We then labeled our -- we then took blood from a recovered COVID-19 patient and labeled those cells with these tagged antigens. From there, we flow sorted out the B cells that were [Audio Gap] on to the antigen and then ran these cells on our single cell immune profiling platform. We were able to use the Feature Barcode sequences on the tag antigens to quantify the binding of these tag antigens to our B cell receptors. And in addition to that, we were also able to capture the paired, full-length T cell receptor sequences from this data. And this data generated what we call a honeycomb plot. This will be a new data type that will be available with BEAM, which allows us to visualize the effects of the binding to these different antigens. So then the honeycomb plot, each dot represents a single cell, [indiscernible] dots represent a clonotype and here, what you can see is that there are -- they were able to detect a range of binding affinity for these B cell receptor sequences for the Cyt protein. Okay. And with that, I'll go ahead and turn it over to Dina.

Thanks, Sam. So Sam covered some new exciting products and capabilities that are layered on top of our immune profiling single cell product. But what I want to talk about today is an entirely new assay chemistry and a brand-new assay that really opens up new single-cell workflow. So we're really excited about this assay called fixed RNA profiling for single cell, and this is expected in the middle of this year. So just to set this up, most of our users use fresh living cells as input into the single cell assays. And this is great. But sometimes there's a lot of constraints around the time that you collect samples to the time that you can process them. And of course, some cells are fragile, some cells are changing rapidly. And sometimes, you need to transport your samples from the site that you collect them maybe to a core facility, a core lab or even just to the lab from an operating room or a blood collection site. And so really, when you start thinking about these larger studies that can include collecting examples from multiple centers, geographically separated or over time, really, we want to enable the use of single cell analysis methods for these types of studies because I think there's so much valuable information that can be gleaned for these types of data sets. So on the next slide, we're excited to announce our fixed RNA profiling assay. And this is an assay that will run exclusively on our Chromium X and iX series of instruments that Sam introduced really nicely. These are really our instruments of the future that not only enable those high throughput assays but also this new type of high-throughput assay for fixed samples. And so this assay, which I'll introduce a little bit today, as I said, it really opens up new types of study designs and unlocks new samples. And it does also really simplify the way that you can batch and multiplex samples together, which further really increases the throughput of the experiments that can be run. And additionally, as I'll show you the design of this assay, as I said, it's a new chemistry, it will really open up a new path on our gene expression road map into the future. So on the next slide, so it is a pro-based assay. It is a discovery tool. So this does cover sort of the whole transcriptome but it does not depend on polyA capture of transcripts as our other gene expression assays do. And in this case, we're using formaldehyde fixation to really lock in the biological space at the time of fixation. And once you fix, you have freedom to store the samples, transport them, wait until a convenient time to batch them or to run the experiment. And once that experiment is ready to start, it uses a probe set that is either specific to human or mouse and each of these will cover over 18,000 genes, human or mouse genes. And those pro pairs allow you to very sensitively detect the genes in these formaldehyde fixed cells. So you might know that fixation can cause some cross-linking, can cause some changes to the molecules inside the cell. So this is a really sensitive way to ensure that we're getting very good gene expression data. And so I'm just showing a little workflow here where the assay is also compatible with multi-omic measurements like cell surface protein measurements. So in that case, you would do the staining for those cells before the fixation. Then you would fix and permeabilize cells, at which point you can store them. And when we release this product, we'll have lots of good data showing storage conditions and what we recommend for keeping those samples impact. And then you proceed with the Chromium workflow on the Chromium X with this brand-new chip and this brand new chemistry. And what you get out is gene expression library that you sequence and you can analyze. And on the next slide, just to show how the data compares to one of our existing gene expression assays. So here, we're showing how it correlates with our 3 prime assay, which you might be familiar with. And on the x-axis of this plot, you can see the 3 prime B3 10x assay that was run with a fresh sample. And this is breast cancer dissociated tumor cells. So on the x-axis, as I said, is the fresh sample run with the 3 prime assay, on the y-axis is the same sample but fixed and run with a fixed RNA assay. And so you can see that the correlation where each of these dots represents 1 gene, the correlation is very high and the fixed assay is very sensitive. And we're showing 4 specific genes in red there that are making nice populations of cell clusters in this sample. So you can see a range of immune cell population and mesenchymal cells. And what you can see is that when we integrate the 2 data sets together, those genes that are marking those clusters are very, very concordantly overlaid. So we're really replicating the same biological insights even though it's an orthogonal chemistry for detection. On the next slide, I also wanted to talk about the multiplexing capability. So because we're using a probe-based assay here, you can actually take advantage of the probes themselves and include a unique barcode. So we have up to 16 individual sets of barcodes that can be combined into 1 lane of the chip. And so what we're showing here is just 3 as an example in this picture. So we're showing 3 tubes with the 3 colors representing different barcodes. And what you do is you label -- you fix, you can store same workflow as before, where you free yourself of the constraints of needing to rush and get those samples processed quickly or drive them quickly to the core lab. And once you're ready to resume the experiment, you would hybridize with those sets of probes. And then you would pool the samples together into 1 lane. So you can, again, run up to 16 in 1 single lane. And then in the final data set, you would de-multiplex all the data where each transcript is labeled with the 10x barcode that tells you, which cells it came from and which probe set it belongs to. So you can really de-multiplex all of that data and run really high throughput experiments. And of course, this also reduces the cost, for example. So here's an example where we took [ 1 ] big PBMC. We split it into 16 individual pools and we ran each of those with the probe set. And then we loaded them together into 1 lane of a chip. So this was showing 80,000 cells. That's not the maximum, but it's just what we did in this case. And so you can show -- you can see the different clusters of immune cells that we are detecting in this PBMC [ plot ]. And on the next slide, we're separating them by probe barcode. And so hopefully, you can see that it's completely identical in each of those little graphs really indicating that there are no batch effects between the different barcodes. And so this is a really great way to increase your throughput, reduce your batch effects or your variability because you can combine samples from different time points, from different experiments and run them all on the same day. So we're really excited about this product, which we feel will really unlock larger studies, more complex study designs and really just relieve a lot of the constraints that people face with single cell workflows today.

So next, we want to talk about ATAC v2. And really, just to understand these regulations, you really need to understand chromatin accessibility. In 2018, we introduced a Single Cell ATAC assay, and this made studies of chromatin accessibility and prescription resolution in single cells possible. So in the middle of this year, what we will be releasing is a version 2 of a Single Cell ATAC workflow. And as what you can see here, this gives a boost to sensitivity of anywhere from 50% to 75% depending on your sample type. This also means that because of the reduced background signal, you can increase the number of [indiscernible] that you can call within your sample, which is shown on the right panel. Next slide, please. So just to recap, ATAC v2 lets you measure chromatin accessibility at single-cell resolution, same that you would be able to measure with ATAC v1. We have an improved signal-to-noise ratio with this kit. So this also means that you're able to get more information compared to -- at the same sequencing depth compared to ATAC v1.1. So if you wanted to, you could also reduce your sequencing depth and save up on that front as well. Along with the release of ATAC v2, we'll also be releasing a software update that enables you to do a batch correction from v1 to v1.2 so that you can analyze them together, which is really important for customers who are doing perhaps longitudinal studies, and they want to switch in the middle of the project to really harness the increased sensitivity. Next slide, please. So on this slide, you really see here that if we take a look at the Human Cell Atlas data portal, the majority of the data derived from [ this ] is about 25%. And this really makes sense, freezing tissue is fast, easy. And as Dina talked about, there are certain constraints with work with fresh tissue. And so freezing this tissue really solves some of these problems associated with transporting and storing fresh tissue. And on top of that, there may be lots of boxes full of archival tissues that are not currently being accessed, [indiscernible] is just due to the complex nuclei isolation workflows that are sometimes complex, both throughput and time consuming will perhaps require additional instrumentation to remove debris and optimize for each individual tissue. Next slide, please. And so I'm very excited to introduce our first single cell sample preparation product, which is the Chromium nuclei isolation kit. And as you can see here, the workflow is pretty simple. You take your tissue of interest, you disassociate it in a Lysis Buffer or pass it through a spin column and then debris removal buffer, followed by subsequent washing steps. And after [ doing the ] wash, they're counted and they're really ready to go at this stage to be loaded in any of our Chromium assays for either gene-expression chromatin accessibility or the combined multiome assay. So again, all you really need is an hour of lab time, a benchtop centrifuge and an interesting frozen sample that you want to analyze with single cell sequencing. Next slide, please. really quickly, just to show how this method compares to existing method, we retested -- nuclei isolated from adult mouse kidney using the Chromium nuclei isolation kit with [indiscernible] nuclei isolation protocol. And you can see through that the increase in [indiscernible] is up to 40%. Next slide, please. And just to quickly show you how this translates into UMI and gene profile, you'll see that increase in terms of genes capture can be up to 20% for the sample type. Next slide, please. And then just to really put this nuclei isolation kit to the test, we wanted to track some real-life samples because you know that's what we will be doing out there in the field. And so here, we went ahead and isolated nuclei from [ 8 ] tumors in parallel under 1 hour. And so you can see here is that we have a wide range of cell types. The majority of these cell types correspond to the primary tumor cells for each of these tumors. But you can also see distinct clusters that represent immune cells, including neutrophils that we can also see normal epithelial cells, endothelial and stroma, really just showing you how this data can capture the overall tumor microenvironment. And on the next slide, what you'll see is that if we just take a look at 2 of these samples, you can see the differences in the tumor biology and really capture -- which is captured by this data. So for example, for these 2 samples, even though the fraction of B cells is very similar to each other, the breast tumor contains a higher fraction of NK cells as compared to the melanoma, which is a higher fraction of monocytes from T cells. And although this is just a few samples, and you definitely need more samples and complete medical history to draw any conclusion from this data. By utilizing this, it's very easy to generate high-quality, high throughput single cell data than it has been before. Next slide, please. And again, just to recap the nuclei isolation kit. This is really meant to standardize nuclei isolation. There is little to no optimization needed for most of these samples. I think and most importantly is to highlight that this kit was built and optimized specifically for 10x Chromium assays, really just to give you the high level of performance that you expect from all our samples. And we're really excited to see how you apply it to the amazing research that you're working with. And then to tie it off with, I just want to just highlight the fact that at 10x Genomics, the single-cell gene expression landscape has really evolved to the point where a single cell is sometimes the de facto standard for analyzing new sample types and approaching new biological questions. And during that time, we've really continued to innovate listening and working with you, our customers, to help [ tools ] that are needed to answer some of these really challenging biological questions. And so as a result of that, there's a wide range of scale, sample types, omics and budget that we have products for to make single cell analysis more accessible for your -- for accelerating your research.

All right. Well, thank you so much, Sam, and Dina for the presentation or the updates on the single cell. So before we move on to the spatial biology, I'd like to hear some of the feedback from the audience. So we mentioned many new products, including fixed RNA gene expression for clinical sample, nuclei isolation that you can use for multiple single cell assays, higher sensitivity ATAC v2, CRISPR now we are enabling for the 5 prime single-cell immuno-profiling solution. Last but not least, we will be preparing for the BEAM. So I'd like to see which products you are interested in from this line up, and this is multi-selection. So if you have any multiple interest then please let us know. So let me stop the poll question and share the results of the gains that we see what type of the products that you are excited about? So fixed RNA really high interest. Good to see the nuclei as well as ATAC, we're very excited about it. And CRISPR is coming up and then as well as the BEAM. Excellent. All right. So let's move on to the second session, which is about the spatial biology. Right. So with that, Jyoti, tell me if you can share the slide.

Yes. Give me just one second.

Cool. All right, it's all yours. Thank you.

Thank you so much, Mio, and thanks to the single cell team for setting up the background for our single cell solutions. So everyone, welcome. My name is Jyoti Sheldon, I'm the Product Marketing Manager for our on-market Visium Solutions. And me and Courtney are going to go over the different Visium as well as our Xenium platform that are now available and some of our upcoming products that will be available later this year. But to get started, as the single cell team clearly pointed out earlier that the various 10x technologies, they're really driving discovery across multiple research areas and that's seen through our various number of locations. Now that driving of discovery and research also holds true for Visium. We've seen over 200 Visium publications as well as preprints. And these publications really form a wide range of applications, all the way from discovery to even translational research. In fact, this year, we were honored to make a cover where Visium was featured on the cover of the Science Translational Medicine Magazine, but also have been listed as 1 of the top 10 innovations in several articles over the last 2 years. And we continuously seem to innovate and improve our products. So to give you guys a little bit of background on what are some of the key features or key characteristics of the Visium Spatial discovery platform. So Visium Spatial discovery allows you to do whole transcriptomic analysis in both FFPE as well as in fresh frozen tissues. It gives you that data at a higher resolution, and it allows you to do true discovery and ask those true discovery questions for your research. It is a kitted and ready-to-use solution. You also get to co-detect both protein as well as RNA or youy whole transcriptomes in the same tissue section. It has an efficient workflow that leads into streamlined data analysis and because 10x as a family aims to deliver everything from single cell to spatial, you get that world-class support. So how does the Visium discovery platform work? Now the Visium discovery platform really allows researchers to map their spatial gene expression data of various complex as well as heterogenous tissue using these Visium slides that utilize polyA capture as well as our novel spatial bar coding technology. Now what you see on the screen here is that a standard Visium gene expression slide, which consists of 4 capture areas. Each of these capture areas consist of about 5,000 barcoded spots. And these spots are about 55 microns in diameter. Now within each of these spots, there are several oligo nuclei types, and these oligonucleotides and these oligonucleotides are made up of multiple components that allow researchers to identify their transcript, count the number of RNA molecules as well as really allow you to find out where those molecules are within the tissue and give you that morphological context. The Visium platform is compatible with both FFPE as well as fresh frozen samples. We launched our FFPE assay last year, and I'm very proud to announce that we just saw the release of our first FFPE publication that came out of Catherine Fridman lab at Cordeliers Research Center. This is a very good publication that really demonstrates the utility of our FFPE Visium assay in revealing and resolving the heterogeneity in renal cell carcinoma. In this particular publication, the researchers used both the Visium's fresh frozen as well as the Visium FFPE assay. And the combined data set from this spatial transcriptomic assay with bulk RNA sequencing as well as protein imaging using immunofluorescence. And with the combination of these 3 techniques, they studied the role of tertiary lymphoid structures or TLS, in how they mediate B-cell maturation and how they produce immunoglobulin producing plasma cells. And overall, how this mechanism then fuels to improve responses for patients to immune checkpoint inhibitors as well as lead to a progression-free survival. So what you see on this slide is a pathologist annotated H&E section in both FFPE as well as frozen samples. And [ CA9 ], which is a tumor marker really allowing them to identify tumors that were TLS positive as well as TLS negative. Once they establish these 2 different tumor types, they then use the Visium assay to really zone in and profile the gene signature for this particular tertiary lymphoid structure. Then after identifying those gene signatures focused and look into phenotyping as well as localizing the B cells as well as plasma cells. They then used robust cell type decomposition, or RCTD, along with single cell sequencing dataset that showed subtypes of B cells from tonsil samples. And so they applied the clusters for those B cells to the Visium data, and they found out that primarily these memory B cells along with plasmablast and plasma cells, should increase expression in that TLS region. Now because publications have shown that plasma cells are responsible for producing antibodies, they also look at the gene expression profile of various immunoglobulin genes. And they saw an increased expression and a dispersed expression of IGHG1 and IGHA1. Now after spatial transcriptomic Visium revealed colocalization of these B cells as well as the plasma cells, this suggested that there was a B cell adaptive immunity generation happening in situ. So then naturally, they wanted to study the B-cell receptor sequences, which get mutated as a result of this immunity generation. And for that also, they were able to combine both RNA sequencing data with data from Visium. And with the power of Visium, they were able to reveal or identify the [ raw ] transcripts of the BCR sequences and found out that there was an increase of heavy-chain clonotypes, along with immunoglobulin in these tumor cells. So overall, they had a lot more findings. But with -- in this paper, with the use of the Visium Fresh Frozen and the FFPE assay, the scientists revealed a mechanism by which TLS mediates the production of B cells and these immunoglobulin producing plasma cells that then produce antibodies that have apoptotic activity and thereby help improve the response to immune checkpoint inhibitors, a very powerful paper. But as excited as we are about our FFPE assay, we are even more excited about our upcoming platforms. So this year alone, we are improving as well as innovating to allow researchers to get access to more samples, more analyte types and see all your data at a higher resolution. We will be launching CytAssist instrument as well as the larger capture area slides and the Visium gene and protein expression assay in the middle of this year, and I will talk about them in a little bit of detail. And then later this year, we will be launching our Visium HD assay, which Courtney will cover in the second part of the presentation. So as we all know that RNA expression truly provides valuable insights into various kind of cell types, states and even revealed our function. But RNA is only part of the story. By adding protein as an additional key analyte, it allows researchers to really understand and characterize itself. An example of such data might be identifying immune cells. These cells often have low expiration or are even post transcriptionally regulated. So really by combining analysis for both RNA and protein can enable users or researchers to get an even better understanding of their tissue architecture, the spatial architecture and its underlying biological function. Our Visium gene and protein product will truly enable you take a microscopic image to an H&E or immunofluorescent image that stained on an FFPE tissue section and then simultaneously profiled RNA and protein in that same section at a high special resolution. This will be an NGS-based antibody readout. And so you really get that freedom to scale to a large number of targets. And because it is NGS-based, you're not limited or constrained by things such as spectral overlap, which is very commonly seen when you use optical dye for protein detection. So how does this product work? It will use our new Visium slides along with DNA barcoded antibodies. Now these antibodies can be bound to specific intracellular or extracellular proteins in the tissues on to the Visium capture slide. The antibody barcodes as well as your transcriptome wide RNA probes are converted into libraries in parallel and in sequence. And then when you do your data analysis, you take the protein and the gene expression data and then you align it with your H&E or immunofluorescent image that you take earlier in the workflow. And as I mentioned before, this will at the end give you that NGS-based readout. So to really kind of demonstrate the power of this and to evaluate the performance of this assay, we work with some reference tissues that have non-morphology as well as distinct expression patterns. So you -- what you're seeing is where we analyze a tonsil section with our Visium gene and protein expression assays using a panel of 20 antibodies. The tonsil, as you know, is an immune organ that shows very clear discernible repetitive structures and it contains a lot of major immune cells. So as you can see in this H&E image, you clearly see those follicular regions that contains major immune cells as well as epithelial layers. But then now we wanted to add another layer, and so we looked at the protein expression. And if you can see the protein expression very clearly correlated with that morphology. And we were able to nicely see those clusters align with the macroscopic structures that we saw with the H&E. But then the power really came in when we added another layer of RNA data, and we saw that same correlation consistent with both protein, RNA as well as H&E. So then we take a look here at sample -- of ovarian cancer sample, where we studied a panel of 25 antibodies. Again, it consists of both intracellular as well as extracellular markers. Now the pathology annotations showed a very visible invasive carcinoma region as well as some immune cells in this section. We saw -- identified 2 compartments of invasive carcinoma, a small invasive carcinoma and a large invasive carcinoma. Now using our protein expression or antibody panel, we first confirmed the presence of those immune cells in the same locations. But additionally, we were able to also subtype these cells based on very characteristic surface markers using our protein panel. And in addition, as you can see here, we saw that the small region of carcinoma that was annotated by the pathologist, it showed a cytotoxic T cell infiltration, but the large carcinoma did not show that. And so to really get that multi-omic readout, we went a step further, and then we added the RNA component, and we compared the gene expression profile of the large as well as the small carcinoma region to really find out what those differences were. And we also saw how they correlated to the very immune cell infiltration that we saw in the protein data. Now as you can clearly see here, we saw an up regulation of this HLA-G, which is an immune response gene in the small carcinoma region, where we saw an increase in cytotoxic T cells, again correlating to the antibody data but then we saw an up regulation of IMPG2, which is known to be involved in tumor growth in that large carcinoma region. So really, again, highlighting the power of combining RNA and protein. Now with that, I want to move on to our next product. As we know that our 10x spatial solutions or discovery platforms, they really combine the power of histology as well as that high-plex molecular readout in the same tissue section. But oftentimes, combining the power of these 2 worlds can involve a lot of logistical challenges because histology labs, they may not always be equipped or even trained to adapt to those tissue preparation workflows for Visium. And then NGS labs may not be comfortable with that. So to truly bridge the gap between these 2 workflows, we will be launching our CytAssist instrument. The CytAssist instrument is a benchtop instrument that will allow users to get that expanded sample accessibility. So you can use H&E or immunofluorescence stain slides. You can also use blocks or pre-sectioned tissues on standard glass slides. It will also [ users ] to have simplified handling because they're not going to need specialized training that it's going to make collaboration between organizations or course easier. But then lastly, it's going to give researchers a freedom of choice, where researchers can now prescreen their tissue sections and then align their tissue so they can focus on regions of biological significance. So taking a look at the CytAssist workflow, the CytAssist workflow is pretty comparable to the current manual workflow, where you do your sample preparation, imaging and probe hybridization off-line. Then inside the instrument, you load your standard glass slides with the Visium capture slide, where the instrument will enable or facilitate permeabilization of your tissue and allow for transfer of either RNA or both RNA and protein analytes to the Visium capture slide, after which your probe extension and library construction happen offline. At launch, this product will be only compatible with our FFPE assays, but we are evaluating other assays down in our road map. [Technical Difficulty] illustration and data that shows you how exactly will this instrument allow you to choose and focus on those regions. We're looking here at a large embryo section and using the window on the instrument and the guide, we are able to focus either on the mass embryo head or the mass embryo torso, really giving you the freedom of choice. And here -- where we're seeing, again, how we were able to precisely target those regions and see those -- that clustering that was obtained from the remainder of the Visium workflow. Now because Visium is -- the CytAssist is an enabler and facilitator for our manual workflow, I just wanted to show you guys this data set that shows that this instrument and the performance has been benchmarked to our existing manual workflow, really showing that we are able to retain the sensitivity and show spatiality comparable to our manual workflow. So really, again, I wanted to highlight the power of this platform to take Visium to that extra step and giving researchers the flexibility in their Visium analysis for FFPE samples. With that, I'm going to hand it over to Courtney, who will cover the other 2 topics. Thank you.

Great. Thank you very much, Jyoti, and hello, everyone. It's nice to be here tonight. And if we go to the next slide, I'd like to focus a little bit now on the higher resolution needs. So as Jyoti mentioned earlier in the presentation, Visium has over 200 publications in preprint. So the platform has really enabled a large variety of important applications and address many research questions. But some of those questions really do need higher resolution include [Technical Difficulty] profiling, developing organs or interrogating the spatial architecture of heterogeneous issues such as the tumor micro environment. And so that's what HD will do. If we just click forward here, with the advantages of the existing Visium technology, which includes full transcriptome profiling, the streamlined workflow and the easy-to-use data analysis tools, HD will take all of that into account and then additional distinguishing factors behind HD will be increased spot density as well as smaller spot size. And so the capture features will be very densely packed and they will be sub 10 microns in size. And so this is what will allow us to truly offer single cell scale data with that spatial context. And so this will really provide unprecedented resolution and tissue coverage, so you can really profile those smaller tissue sections, the developing organs, again, highly heterogeneous tissues. And so to achieve this massive [ jump in ] resolution, we're developing a completely new slide architecture, what we show here is a mouse eye, which really helps give the feel of the scale of HD. So you can see how that resolution and expanded tissue coverage of the more compacted spots for HD will allow precise identification of the layers within the eye and then even the cellular composition within a single layer. And then on the next slide, I'd like to highlight our breast cancer section, where, again, by using this very high-resolution HD assay, we can really finally resolve that tumor border and also select 2 different regions. So what we show here on the left-hand side is an invasive carcinoma. And then on the right-hand side is a ductal carcinoma in situ. And again, just with the way the Visium assay as a whole works is that you get that entire tissue section coverage, not just a few artery regions, you can really look at the entire tissue section and analyze any of that section in the data analysis after the experiment. And so the same will be true. Again, with HD, you'll be able to profile the whole transcriptome in these entire tissue sections at that single cell scale and with that expanded tissue coverage. And so we're expecting to release this later this year. And so we're really excited to provide this capability to you and to see all the new applications that it will enable. And so with that, just to summarize the Visium platform that Jyoti has mentioned and highlighted, with Visium as a whole with all of these new capabilities that we're going to be unleashing, you'll be able to detect more analytes, more samples and do this at higher resolution. As we mentioned, the gene and protein assay will be -- and CytAssist instrument will be released in the middle of this year, and HD will be released later this year. And so with that now, I'd like to then switch gears from Visium and then talk about our new in situ platform and some of the developments happening there. So we've already heard from the Chromium side and the Visium side, these 2 platforms really continue to push the boundaries and the frontiers of cell and tissue research. These 2 platforms are ideal discovery tools. They measure the entire transcriptome of sample, you can identify cell type markers, cell composition, regional gene expression, again, all with an unbiased whole transcriptome approach and with a sequencing read out. But with -- in situ, with all of this information, we now -- a natural follow-up question is going to be [Audio Gap] cells exactly located, what specific combination of markers can be found in a single cell? And where is that cell located? And that's really where Xenium comes in. This platform will deliver targeted gene expression information at subcellular resolution and with high sensitivity. So we'll have platforms ranging from discovery, that can then help fuel and feed into in situ targeted panels. And on the next slide, we can highlight our new instruments. So this is the Xenium In Situ platform. And it really will take in situ analysis to a new level. So as traditional in situ, you're only looking at a handful of genes. But with Xenium, you'll be able to use gene panels that will comprise of hundreds of targets and our road map plans to extend to 1,000-plus targets in the future. This platform will also enable simultaneous profiling of both RNA and protein in the same tissue section. So you get a really much more complete picture of the biology that's happening on the tissue slide. And in addition, we'll support both fresh frozen and FFPE tissues, and have the throughput capability to support large cohort studies. And on the next slide here, we can show you just a quick look at how the Xenium workflow actually works. So starting with sample preparation, which includes permeabilization and hybridization of our circular DNA probes and those probes have a gene-specific barcode. After the sample prep, the sections are then loaded onto the instrument and the tissues undergo cyclic rounds of fluorescent hybridization and imaging. And this is how we can generate an optical signature for each gene, which is then used to construct the spatial map of the transcripts across the tissue section at a subcellular level. And then following that, secondary analysis and visualization is all done off the instrument. And here on the next slide, we have an example of some early R&D gene expression data using Xenium on an FFPE human breast cancer section. So on the left, we show an H&E image. This is annotated by a pathologist, which identified invasive carcinoma, surrounded by fibrous tissue, adipose tissue as well as tumor necrosis. And then on the right-hand side, we have the corresponding gene expression in situ image that was generated by Xenium looking at over 200 RNA targets. And if we compare the annotated H&E section with the corresponding Xenium in situ image, we can see that there is a strong spatial correlation between the distribution of the cell types and the pathologist annotations. We also took it a step further and also compared it to our Visium assay. And so we wanted to get the spatial distribution that we see with Visium as well as with Xenium. And we see a very strong correlation between the spatial distribution of the cell types that we obtained -- cell type and genes obtained with Visium, which was detected through NGS sequencing, and that's in the middle panel. And then Xenium, which was detected by microscopy with that subcellular resolution. And in this particular example, we honed in on 1 gene, ERBB2, which encodes HER2 and we can see that this is indeed a HER2 positive breast cancer tumor. Now in addition, as I mentioned, we can also detect proteins as Xenium. So we examined another breast cancer sample, and we used DNA barcoded antibodies in addition to RNA labeling. After we finished multiple cycles of RNA decoding, we also imaged the DNA barcoded antibodies. And that allowed us, in this particular example with a combination of antibodies shown here on the screen to identify cells of epithelial and mesenchymal origin. And during this process, tissue morphology and [Technical Difficulty] are well preserved even after several cycles of RNA decoding. And then finally, I just wanted to highlight the resolution of Xenium. So showing here because of that high resolution, we can really start to zoom into specific regions of the tissue and identify key biological events such as immune infiltration into the tumor. So what we show here is an H&E stain on the left, where we can see a few interesting cell types by eye. When we look at the molecular profiling, we actually can identify some rare immune cells that are in close proximity to the tumor region. And this could be clinically relevant and important for development of immunotherapies in cancer research. And so overall, Xenium will be a complete platform that includes a versatile instrument, consumables, panels and software, and it comes with the full support of 10x Genomics expertise all the way from tissue prep to data analysis. And the initial commercial release of our Xenium platform is expected later this year. And this is just the beginning of the Xenium road map, like Chromium and Visium, we'll continue to build this solid foundation with enhancements on core capabilities, adding more panels, more analytes and a whole suite of new software tools and other features. And so in conclusion, the 3 platforms at the core of 10x Genomics technologies are really driving research all the way from discovery to very targeted focused research. Our Chromium platform is the ultimate single cell analysis workflow for dissociated samples. Visium is our spatial discovery platform of choice, allowing whole transcriptome profiling of tissue sections and Xenium, our upcoming in situ platform will provide the highest spatial resolution across many sample types really enabling translational and ultimately, clinically relevant applications with this focused approach. And so thank you very much for your attention, and I will turn it over to Mio now.

Thank you, Jyoti and Courtney. Just a reminder that we're actually having a separate webinar session coming up for April -- in April for some of the products. So if you are interested in, please scan or type this URL for the registration. So we are going to the Q&A session. But before the -- we see single cell product line, I'd like to hear the audience interest on the spatial biology. So we mentioned about Visium core detection of gene expression and protein expression. Visium CytAssist, so that you can transfer the slide, FFPE slide to the Visium slide or high-density Visium HD. Last but not least, Xenium in situ platform, which is new capability outside of the next-generation sequencer. So let's see how it goes, getting some -- okay. Let me finish the poll and then share the information. So high interest in the core detection on gene expression and protein, which is great. And also high interest on the Xenium platform. So thank you very much for your interest. And we are going to the Q&A session.

So if you have any questions, please submit through the Q&A chat box. But I also leave this 1 open. If you want to have a private discussion with us for the pricing of the products that we have mentioned or some of the technical question, just answer this, and then we'll follow up with you later. Right. So with that, we have a few questions for the single cell. So let's try this one. So I am trying to use single cell RNA sequencing. How could I narrow down the type of single-cell RNA sequencing. For example, [ 3 dash ] gene expression or [ 5 dash ] Feature Barcoding.

Yes. So I can take that one. So it's a great question, I think, especially as we have more and more single cell gene expression assays, it definitely can get a little bit trickier to narrow down and figure out exactly which 1 is best suited for your sample type. And so actually, with the release of the fixed assay, we will be providing kind of like some guidance like a little flow chart that helps you decide basically which single cell assay is going to be most appropriate for the work that you're doing, but you can imagine that there are a couple of factors that play into it. So species is a big one. Our fixed assay is going to be probe based. So it will be compatible with human and mouse. So if you're working with nonhuman nonmouse species, it would be better to go with 3 prime or 5 prime. And then also the requirements for your analytes will also be important. So for example, if you want V(D)J receptor sequences, and thus that situation I definitely recommend going with our 5 prime assay as the primary assay of choice. As I said, we'll provide more specific guidance closer to the launch of fixed, but those are just a couple of key considerations to take into account. And any 10x Genomics representatives can walk you through that.

Thanks, Sam. Let's go to the next question about nuclei isolation kit. We need to purify nuclei by FACS when we use the nuclei isolation kits?

That's a really good question, and I think I'm very excited to tell you that the answer is no. So when I showed you a little bit of the workflow, you'll see that, again, you're disassociating your tissue, you're passing it through the spin column, there is a debris removal buffer step that helps you get rid of some of the debris there, and there are additional washes. So the combination of those 3 steps helps remove most of the debris present within your sample. So for all the sample types that we've tried in house and these ranges from human tumors to like about 20 mouse tissues, we haven't had to use FACS for a cleanup, the results that we get from using the -- and the protocol is pretty clean. If there are some debris present, these tend to be pretty small and really not impactful to the data.

Thank you, Zuley. Next question is about fixed RNA. May I clarify that the fixed RNA solution is comfortable with cell surface protein providing the molecular [Technical Difficulty] of the antibody derived packs be different from the current 3 prime and 5 prime solution?

Yes. That's a good question, and I'm happy to clarify. So it will be compatible with cell surface protein, and that will be using the TotalSeq-B group of antibodies that are conjugated to an oligo that it's the same group that's compatible with our 3 prime gene expression products. The only thing to keep in mind is that to run cell surface protein with this assay, you will run it in a single plex format. So in other words, 1 sample per lane, if you want the self surface protein. If you are interested in gene expression only, you can multiplex multiple samples per lane.

Thank you. Let's move on to the spatial questions. So could you describe predesigned panel composition?

Yes, I can take that. I think I can speak to both from -- there's the protein and the Xenium side. And with both of those, the composition, we're still working on the finalization of what exactly will be in those panels. But what we do to take into account, particularly for the Xenium platform is leveraging what's in the literature, what we know are key targets or proteins that are related for cell typing, cell markers, also taking into account the discoveries that we're learning, again, from tenchiques like Chromium and Visium and those discovery applications to fuel the panel development and then also taking into account researchers and what their needs and parkers are. And so we would also love to hear from you and what you would also like to see in the panel as well.

Thanks, Courtney. Let's go to the CytAssist question. Can you use IHC stain sample with CytAssist?

Yes, I can answer that one. So at the moment, CytAssist will only be compatible with either H&E or immunofluorescence stain samples, primarily because IF staining can be quite aggressive on the tissue and can damage RNA quality. So it will only be compatible with H&E or immunofluorescence, not IHC or DAB staining.

Thanks, Jyoti. We have 2 questions on -- sorry, 1 question on the Xenium. Will Xenium be comfortable with FFPE samples?

Yes, it will, both FFPE and fresh frozen samples.

Right. Going back to the Visium spatial gene and protein expression, how many protein targets will you be able to look at?

Okay. So let's see, with this -- again, as I mentioned earlier with the panel, we're still really finalizing the panel, and we'll release more information closer to launch. But now we've tested dozens of markers. As Jyoti showed earlier, panels of 25 proteins, but we've tested even more than that. And so again, we're still finalizing the final content but it will be dozens of markers in that final panel.

Thanks, Courtney. Let's take the last question. going back to single cell nuclei. Nuclei isolation kit is compatible with all the Chromium assay, including high throughput?

Yes. So you can take the nuclei for isolate using the nuclei isolation [Technical Difficulty] I think the -- 1 of the things about this kit is you can process a bunch of samples in parallel, so you can process up to 8 in an hour, and this makes higher throughput experiments utilizing some of the HD capability possible.

Right. I think we covered most of the questions here. Sorry that we are 10 minutes late for the finishing time. But thank you very much for all the speakers for the update. And thank you, everyone for great questions. And the recording of this webinar will be available next week. And with that, I'd like to finish the session. Thank you very much, and see you next time.