DeciBio Q&A

DeciBio’s Single Cell Multiomic Q&A with Anjali Pradhan of Mission Bio

October 18, 2021
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We’re at a fascinating time in biology. Recent innovations like next generation sequencing (NGS), CRISPR, spatial omics, and single cell are enabling researchers to interrogate biological systems with an unprecedented level of precision. Single cell approaches are uniquely positioned to revolutionize biology by shedding light on cellular heterogeneity, which has important implications for disease. One of the companies leading the charge in single cell DNA and multiomic approaches is Mission Bio, which raised a $70M Series C round in August 2020 led by Novo Holdings.

We caught up with Anjali Pradhan, the Vice President of Product Management at Mission Bio to hear more about recent developments at the company. Anjali brings a wealth of experience to Mission Bio with over 15 years in the life science industry focused on product development and commercialization. She has been instrumental in the launch of cutting-edge products in DNA sequencing, RNA ISH, and multiplexed tissue imaging.

Anjali, thanks for taking the time to speak with me today. For our readers who are less familiar, tell us about Mission Bio.

Mission Bio started in the single cell DNA space and has expanded into the single cell multi-omics market landscape, which we’re particularly proud of. What that means is our platform is being used by academia and pharma as a life sciences tool for targeted discoveries in translational research. Mission Bio has evolved over time to focus on oncology where we believe single cell DNA multiomics tools can help empower the methods and solutions to improve targeted therapies in curing cancer. We're also seeing entry into rare disease areas and we’re moving into application areas where we're providing novel solutions for therapeutics.

You talked about how Mission Bio has evolved over time, and we’ve seen that with the flagship product, the Tapestri platform. Can you talk about the platform’s evolution and where and how it’s being used?

We started off with the Tapestri as a single cell DNA technology and now we’re evolving into a solutions provider. We’ve established a strong footprint in hematologic oncology (heme-onc) market. We don’t just have the platform; we also have solutions. Solutions for custom and catalog designs for leukemia panels. We've also enabled our customers with Tapestri Designer to design their own panels. On the backend we've built software solutions and tools to provide insights and really to answer a biological question. What you'll start to see from Mission Bio is progression in oncology with other cancer types beyond heme-onc as well as more activity in the cell and gene therapy space.

As for the platform capabilities, we’ve had overall chemistry performance improvements over time. We recently announced the ability to gain insights starting with as few as 20,000 cells. We continue to update our panels and content as well as. Earlier this year we pushed out updates on our pipeline, which enables our customers to analyze and get data from the system faster.

I really like the framing of being a solutions provider. We’re seeing how important that is particularly for adoption of novel life science tools. You mentioned getting insights from fewer cells. What do you think opening up that lower end of the spectrum does for the market?

Yeah, absolutely. Let's just take heme-onc as an example. We are in a space where many of our researchers are MDs, and their labs are working quite often with retrospective patient samples. These patient samples are very precious and many times they have a limited amount of sample because they're doing different types of analysis with it. Enabling insights from fewer cells helps those researchers to get the Tapestri single cell DNA or DNA + Protein information, while still doing other analysis as well. That was a key driver for us to enable that type of capability, especially within the translational clinical space. You can input now anywhere from 20,000 to 100,000 cells enabling researchers to use their different samples.

One of the things we've tracked with respect to technical capabilities is capture efficiency. It seems to have been a key element for 10X Genomics and probably one of the reasons Bio-Rad’s ddSEQ never gained significant traction in the market. What’s the capture efficiency of the Tapestri? Does it matter in the DNA field as much as it does in the RNA field?

In a broader single cell market people do look at capture efficiency as a key feature. I would say yes it matters and people do care. Because we’re focused on the translational space, what we have learned from our customers is that helping them answer and get closer to their scientific end goal is more important. What does their single cell data really mean? So, if we give them a large number of cells, what does that do -- are we getting them an answer or is it frankly making their analysis harder? Can they interpret that data? So, we're focused more on, what's your scientific question and are we helping you get that answer? We’ll continue to evolve our capture efficiency capabilities, but our focus is more about the application area, the multiomic capability and how that data enables our customers to understand their biological question.

You touched on it a couple of times, and you said it’s something that Mission Bio is quite proud of its multiomics capability, which in your case is the ability to look at DNA and protein. What's driving that focus, is it product fit, market fit, unmet need?

I think it's a perfect triangulation of an unmet market need. When you're dealing in AML or heme-oncology, what researchers have talked about for years is the data analysis and the complications that occur because you're not able to correlate the mutation genotype to the immunophenotype. It really is important to understand the order in which those mutations were acquired. What role did that have on the immunophenotype? How does the mechanism of action inform drug resistance? And so, to answer your question, it's a combination of our capability as a technology platform and the unmet market need. Because of our microfluidics technology we're able to give direct correlation between the genotype and phenotype within the same cell. That was a critical piece. It's not like assessing them independently and then going back to infer the correlation via bioinformatics. The way researchers have been studying these diseases is to do different single modal analysis with NGS and flow and then try to interpret the data. Whereas with our platform, you're getting back single cell multiomics data format in in one run. That is very powerful for them to interpret and to appreciate.

Yeah, we’re definitely seeing excitement about being able to assess multiple analytes and it feels like it happened so quickly. Single cell just emerged and now we’re already seeing this added layer of innovation with researchers looking at DNA and protein, RNA and protein, and RNA and chromatin accessibility. Exciting times. I know it’s relatively early, but what are some of the exciting things that are coming out of the multiomic approach?

One of the key areas you'll see through our press releases and publications is the work that our customers are doing in therapy resistance. What we're seeing is researchers really driving towards understanding the underlying cause of resistance with single cell multi-omics. There was a recent publication, by Doctor Chris Hourigan’s lab at NHBLI. They showed the ability to distinguish leukemic cells from CHIP clones - clonal hematopoiesis of indeterminate potential. That's critical because with growth in research towards personalized medicine you're always trying to improve patient treatment. So, understanding the difference between genetic mutations associated with AML for example versus those that occur naturally with age-related clonal hematopoiesis can be critical for accurate disease monitoring and treatment decisions.

There are also exciting publications that have come up that show the implication in minimal residual disease (MRD). This is another area where researchers are doing NGS one side and flow cytometry on the other. This is another instance where the ability to look at the genotype and phenotype in combination could be very powerful; this could be an exciting area for single cell multiomics.  

In addition, there's a whole evolution of targeted therapies, combination therapies, dynamic therapies, where researchers want to improve patient outcome and adjust the treatment based on mutational profiling. If you can see and track residual clones earlier versus six months down the road when they can potentially relapse, that is extremely powerful to help alter the treatment paradigm. We’ve shown we can track sub-clones down to 0.2%. We’re excited to see how researchers are leveraging our platform to inform and improve targeted therapies.

You mentioned people are doing these things independently by NGS and flow cytometry. When you take a single cell multiomic approach are you getting the same level of depth?

The basic comparison is if with bulk sequencing you'll observe mutations, but not at the cellular resolution. The biggest value add for the single cell multiomic approach is the depth of the clonal heterogeneity and subcellular populations. For example, for AML, with FLT3, there can be heterogeneity within those mutations. We’ve seen single FLT3 clones evolve into three different sub-clones by the time the treatment progresses, which can impact treatment decisions. This is the added complexity we're giving with single cell versus NGS. Often it’s the depth of the single-cell information that scientists are really looking for to understand, why did that relapse occur? What happened?

Agreed. We’re seeing a lot of these emerging technologies being leveraged on retrospective samples to see if any differences can be identified in responders vs. non responders to treatment. You talked about Mission Bio’s technology being used in the translational and biopharma settings. We see the technology as being well suited to that market given its targeted nature. How are these customers leveraging your platform?

There are three avenues of engagement that we're seeing. A lot of our comprehensive cancer centers work directly with pharma. UCSF, MSKCC, all these large cancer centers are working with some sponsorship from pharma and getting samples from pharma, so that's one avenue. The second avenue is direct utilization of the platform by pharma. As these drugs are on the market for AML or ALL, there are retrospective studies being done with the pharma clients to understand mechanisms of action. We have a publication with Agios, along those lines. The third piece is our pharma assay development or PAD team, which works directly with pharma clients. Many of these clients have not fully comprehended single cell and single cell DNA. So, this enables them to conduct proof-of-concept studies that they can do with us to see the impact of the single cell study related to their research like understanding mechanism of action. I think each of these is critical for us to engage with pharma.

You touched on retrospective samples. Are you seeing any usage in clinical trials as exploratory end points? Do you see a companion diagnostic in Mission Bio’s future?

I think we're starting to see early exploratory studies, but  it will take some time to get into prospective trials. I would love to see a companion diagnostic. In my experience these things can happen quickly as soon as someone recognizes the immediate impact and value of the technology. I am positive that we'll see something in a short time.

I know it’s probably far down the road, but what potential clinical applications are you seeing?

With the publications that have come out on CHIP and MRD, there's definitely an angle there. And there is another paper coming out soon with clinical implications as well. I think we're going to start seeing some of our customers work in these areas. We as a company are always willing to support, especially on the data analysis and interpretation side to provide answers effectively and efficiently.

We talked a lot about the hematological cancers, where clonal heterogeneity is critical. That’s a very clear use case. What are some of the other applications that you're seeing coming up that could drive growth?

What is exciting for us is cell and gene therapy. It is a fast-growing market, >30% CAGR. We’re starting to see a lot of traction in our pharma services group with some of these clients. Specifically, those who are working with viral vectors and want to understand how well that integration happened. In fact, we just announced a new product offering for deep, simultaneous analytical genotype and phenotype characterization for cell and gene therapies. If I had to summarize, I’d say we’re at an exciting spot with single cell DNA and our ability to customize it for different vectors to give researchers the depth of characterization they need with a single platform. We can give them transduction efficiency, vector copy number, and integration sites, versus what they do today with multiple technologies like PCR or flow cytometry or NGS. There is a trend right now in the market of really better understanding safety and efficacy around these drug trials. Where and when did mutations occur? Did they occur before treatment after treatment? It’s an exciting space for Mission Bio and all of us to really help these customers work on the safety profile of their products.

That makes a lot of sense, and it seems another application that’s a great market fit for your platform. Speaking more broadly how much runway is there for the single cell approach and what are some of the barriers of broader adoption?  

The single cell space is at a very exciting time point. There's been so much sequencing data at the bulk level and now you're going to see that trend at the single cell level. I think we're just scratching the surface in terms of opportunities for market growth. The barriers I think in all technologies are always helping customers interpret the data. How well you can help them interpret helps them get faster to the next project and the next project, so that’s a focus for us. We're continuing to provide end-to-end solutions, making sure we understand the why before we provide the answer. This is going to be critical for us to grow as a company. Exciting times. It’s fun to work with our customers and hear more about their novel applications. I think there's a lot of opportunity for growth.

I agree with you there. We’ve been tracking the space and there’s a lot of excitement. The emergence of new applications new approaches is astonishing. There’s a nature article that describes endless single cell approaches. Well, the market seems poised for more growth. What are the next areas of growth for Mission Bio?

You'll see us expanding across the globe. Growth in terms of the company, the expansion of our platform, the innovation around our platform, and then the markets. You’ll see us having a market and application focus because we're not a discovery tool, so we understand and appreciate that. So, keeping that in mind that prioritizing those markets and applications will be key.

Well thanks for your time today and answering our questions, Anjali. We’re excited to see the next phase of growth at Mission Bio!

Post interview researchers from St. Jude’s and an international consortium published a study demonstrating the utility of single cell DNA sequencing to track clones in children with myelodysplastic syndrome (MDS). Using the Tapestri platform the researchers identified a “battle of clones competing for dominance in the blood system”, with important implications for treatment – early identification of certain self-correcting cells may allow some patients to delay or avoid bone marrow transplants altogether.

Authors
Miguel Edwards
Principal
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