DeciBio Q&A

DeciBio's Spatial Omics Q&A with Ben Hindson, CSO for 10x Genomics

August 25, 2021
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On February 24th, 10x Genomics hosted their first Xperience event, which showcased the next wave of innovations for their three product verticals: Chromium, Visium, and the upcoming in situ platform. If you missed the event, you can find the details here. After Xperience, I had the opportunity to catch up with Ben Hindson to discuss the announcements and updates, his views on the spatial omics industry overall, how he continues to drive innovations in the life sciences, and how 10x Genomics is just getting started. You can find a transcript of our discussion below.

Ben Hindson, Ph.D. is the Co-Founder, Chief Scientific Officer, and President of 10x Genomics. In the nine years Ben has helped lead 10x, the company has brought industry-leading technologies to the market for single cell sequencing and spatial transcriptomics. Prior to co-founding 10x Genomics, Ben co-founded QuantaLife, a biotechnology company which was acquired by Bio-Rad in 2011.

Thinking about Visium and thinking back to 2018 when Spatial Transcriptomics was acquired, and maybe to provide some extra context to readers more unfamiliar with spatial omics, what was the opportunity you and 10x Genomics saw in Spatial Transcriptomics?

At that time there was a lot of excitement and growth around single cell analysis. A lot of great discoveries were made, new cell types, but obviously when you dissociate tissues in that way, you lose a lot of interesting information that is natural to the state of the tissue. We had also been looking at what was next for single cell analysis through a lot of conferences and meetings. There was great interest in determining where are these cells, how are they organized in a tissue, and that is where we saw an opportunity for another pillar of our business. That is what later became Visium. We had looked around at different technologies, and we came across Spatial Transcriptomics, which was developed at Sweden’s SciLifeLab. After some time, we were able to purchase the company and we took about a year to put our 10x touch on it.That was when we entered the spatial market. We see single cell and spatial analysis as very complementary to each other, and one can be used to inform and improve the other, and vice versa. We are always looking to the horizon, and spatial at that time, 2018, was definitely something that was grabbing the attention of key thought leaders. There was the opportunity to get beyond the 3-4 markers with highly complicated workflows and create a platform that would enable unbiased discovery through intact tissues. We were able to act on this opportunity and it’s why we continue to invest in Visium.

Well, with all the announcements made on Wednesday this is definitely the case with Visium HD and proteomics coming online in the near future. You mentioned a few potential applications, and you see Visium adding value to 10x Genomics’ single cell platform and vice versa. Are there any other key areas where getting this spatial context can be a major added value?

I think in cancer research this added context is critical, and it’s also been critical in aspects of COVID research that’s been going on in order to map out what is happening at the fundamental, molecular level. It takes out the guesswork when you have unbiased approaches to discover things you may not have been able to explain before. There is a lot of opportunity for discovering new biomarkers and looking into why certain treatments work. A picture tells a thousand words, and you can see where cells are infiltrating or not, and you can start to get at the mechanisms of these treatments. There is just so much happening in the tumor microenvironment and there is so much heterogeneity within them. As we improve our cell atlassing capabilities, the overall picture for these diseases becomes much clearer.That was where Visium started and that was our interest, and now, just like anything we do at 10x, we always want to improve resolution, scale, and make it accessible to all of our different customers. We want to be able to provide solutions for all different kinds of sample types and researchers. I think one of the key things you picked up on at Xperience is the excitement around Visium for FFPE.

Definitely, and FFPE, considering it is what is being used to biobank a large number of clinical samples, is a key sample type for Visium to grow into when that launches this year. I know you mentioned oncology and COVID as key areas—two clinical applications. Some players in the space have estimated the total addressable market (TAM) for spatial omics to be in the range of $10B, with around half of that in the clinical setting. Considering this, what’s your take on that market size?

Before we get to that, there’s also been a huge uptake in neuroscience. The kinds of information Visium is able to provide is critical for understanding diseases like Alzheimer's and Parkinson's. It’s allowing for us to have a better understanding of pathology and neuroscience, which are rapidly growing areas for these spatial approaches.So, with respect to the addressable market, Serge talked about some of this at J.P. Morgan. We have our own internal estimates around a $15B market we can immediately address and a life sciences market at $60B. Putting in situ on top of that, we think we could add another $10B. It’s still early and there’s still a lot of opportunities and developments, but we think there’s a huge opportunity regarding market size.

It’s obviously an exciting, early market with a lot of growth potential. Thinking about the market, there seems to be a bit of a bifurcation between high-resolution proteomics platforms and high-plex transcriptomics platforms like Visium today. Would you agree with this statement? How do you see the dichotomy between high-plex protein analysis and spatial transcriptomics playing out as 10x Genomics releases Visium Spatial Proteomics as well?

We may have slightly different views on this, as instead of diverging we actually see it as converging. More and more of our customers are asking for MultiOmic solutions instead of just one or the other, and so we’ve already started on this journey of MutliOmics. I think it’s still in the early days and there are lots of improvements we can make on content on both sides. We are going to be working on integrating things so that you can get the most valuable measurements out of each sample at one time. That’s our goal. That’s the whole aspiration for MultiOmics.

This space has been attracting a large number of competitors. In addition to the differences which will drive Visium’s value on its own, in what ways do you see Chromium and the future in situ platform adding value around Visium?

There are some natural advantages to Visium, as it is today, and with what we have announced. I think one of the key pieces that was missing was the FFPE compatibility, and that’s something we’re really excited to get out there. Improving resolution was also something we had heard from the beginning, but that’s not for everyone, so there are different tiers to what customers will need. Like I had mentioned, adding the highly multiplexed protein is also something we are committed to getting out on the market for Visium. Wrapping all of these together into a complete solution includes integrated software, pipelines, visualization tools, and collaborative environments. We think Visium, just like we have for Chromium and single cell, should become the standard. There are competitors, and competition can drive awareness, but we’re going to continue delivering on our promises to our customers as we have done in the past.

So, 10x Genomics is obviously uniquely positioned with the company’s continued leadership position in the single cell sequencing space and also now as one of the key players in spatial biology. Thinking about the two platforms you have today and your future in situ platform, how important do you think MultiOmic analysis will become for these spatial technologies?

As we have touched on, I think it is essential. Samples are the most precious part. They’re very hard to get, and you want to make sure you can extract the most useful information out of each one. I believe the way you do that is with MultiOmics. You can’t get everything from an RNA assay, an immunoassay, or an ATAC-seq assay. On the single cell front, when we combined gene expression with ATAC-seq, customers loved that product, and it was able to generate new insights you couldn’t see before. Customers are already doing it—they are all very creative. We are dedicated to MultiOmics, and we’ve had a good experience implementing it thus far and plan to continue to integrate technologies.These technologies can also work well at different stages. You start up front with discovery doing single cell analysis, with Visium you can start to map where those cells are, and you can imagine a world with in situ analysis where you can have a turnkey pathologists’ instrument. One of the advantages of Visium is, as we’ve seen with the fairly rapid adoption, the limited amount of CapEx needed for it. The barrier to entry is fairly small. With that said, I think there is still an opportunity to continue to help the customer with products like CytAssist to process samples more effectively.

People are definitely well aware of the high costs of a lot of these instruments, and I definitely remember when Visium was first announced that NGS instruments are virtually everywhere already and Visium enables so much more research to be done at a lower cost. Focusing in on something you just mentioned, looking at the clinical space and pathologists for the future in situ platform and products like Visium, how do you see these platforms transitioning into the clinic? Obviously as we’ve discussed the market really caters to early-stage discovery today, but with products launching like the CytAssist, what else can be done to ensure these technologies ultimately impact the clinic?

Well, I think it is going to take time. These things always do. We are engaging with the translational research customers out there, and we have set up our Clinical Translational Research Network (CTRN). There is a lot of interest in the network. It’s partly learning what is needed from our customers in this space and factoring that into our roadmap for what we develop and when. And it’s all still pretty new, right? It’s easy to forget how new a lot of these tools are, and it takes time for them to dissipate into clinical studies. We are seeing this happen, but it does take time. Ultimately, we think there is huge value in a lot of the tools being used for research. I think these are just paving the way for what will be the future of pathology. It will take us a little bit of time to get there, and we’ll take that journey alongside our customers to make sure we’re applying the right efforts in the right places at the right times.

Maybe thinking about that roadmap, what are some of the key challenges that still need to be addressed not only for clinical customers, but also academic and other customers when it comes to things like bioinformatics or the technical aspects of these platforms?

So obviously there are key challenges that remain, which is great because it means we still have a lot of work left to do. Scaling is something that we have focused on, whether that is higher-throughput analysis on the single cell front and making it more affordable for those higher-throughput customers, but then also being able to supply a lower-cost, lower-throughput solutions. It allows you to do pilot studies and get dialed in before you graduate to the next level. It was something that we heard as a need and it’s something we developed and talked about at Xperience.On the informatics side of things, there are great tools that get developed in the academic setting, but it’s also difficult for someone, say, like me who doesn’t know how to write code, getting to the command line because I’m more of a chemist by background. Providing these tools which enable anyone, essentially, to perform these experiments, take data and run it through the pipelines, and do that in such a way where you can look at your biology on a laptop—that’s accessible to everybody. That’s what I think is the cool thing about launching the 10x Genomics Cloud. It’s really geared towards that. You don’t need the computer infrastructure to run the complex analysis. The cloud analysis is a tool which has really wrapped together our vision for providing complete solutions to our customers. We don’t want that to be a bottleneck. There’s a lot of data, it’s getting more and more complicated, and it’s getting more and more intertwined with MultiOmics. The need for these solutions is only going to increase with time. We’re going to keep building tools that bring all of this together so that you don’t get stuck somewhere in the process, and you can get to your insights and move onto your next set of experiments. It’s a difficult thing to do, but we continue to invest in our computational pipelines and software suite. The Cloud is a nice addition to that, and it’s only going to get more sophisticated with time.

Definitely, because today it is focused on the single cell analysis side but bringing in things like spatial gene expression capabilities will be a big value add. On top of that, though, you also have products like the Loupe Browser, which was shown at Xperience, and it has been made obvious this is a key area you are focusing on in addition to delivering the instruments. To wrap up, I’d like to ask a more general question. 10x Genomics, founded in 2012, how do you ensure the company continues to drive innovations as the company grows and nears the end of its first decade?

Yeah, well I can’t believe it’s been almost that long. It makes me feel like I’m even older than I’m feeling right now. Wow! Well, we constantly tell ourselves that we’re just at the beginning even though we have been at this for close to a decade. That starts with our mission, which we’re very passionate about. We want to master biology to advance human health, and in order to do that we have been building these platforms that enable us to measure biology at a fundamental level. In order to do this and continue to do this, it really starts with the people at 10x. They are our number one priority because they are the people that make the magic happen, and we need to keep that as part of our blood and as part of our culture. The people are what make it happen. From there, we also have a lot of great people who are really smart and very inventive, and we have to give them the runway to develop their ideas and new products.We also don’t have a “not invented here” mentality. We’re always on the lookout for what else is happening out there in the field. Maybe there are some new opportunities or new companies that would be nice if we were able to acquire them into 10x. You saw some of those happen last year with CartaNA AB and ReadCoor, and more recently Tetramer Shop. We have got some great people who evaluate what is on the horizon, who scout around and look for things, but one of the nice things about having a good relationship with our customers is that they can also come to us. We provide forums for us to interact and learn, and if there is a new opportunity we can engage. If there is feedback, good or bad, we can address that. I think that is one of the nice things we have been able to enjoy, this relationship with our customers that supports this level of engagement. They are all very smart and understand the biology and their applications’ space extremely well. We just want to systematically look through as much of that as we can and prioritize what we think can fit with our roadmap going forward. Even though it has been 10 years it feels like we are just getting going. We are just getting started!

Authors
Max Jorgensen
Associate & MarketBook Manager
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