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August 25, 2022 by Elise Morrison 11 min read

On the Drop with Nicole Ovadia

In our latest episode of On the Drop, Director of Product Development Nicole Ovadia discusses why measurable residual disease (MRD) is an issue and how our Tapestri scMRD Assay for AML can impact a patient’s journey.

Ania Wronski: Hi, everyone. My name’s Ania Wronski, and I am your host for the Mission Bio podcast. I am very excited to be joined by Nicole Ovadia, who is our Director of Product Management here at Mission Bio. She’s recently joined us to lead a very, very exciting project, so welcome, Nicole.

Nicole Ovadia: Hi. Thanks, Ania. Glad to be here.

Ania: So I know it’s a very exciting time. I know you’re very busy, so why don’t we jump right in? Can you tell us a little bit about what you’re working on at the moment?

Nicole: So, here at Mission Bio, I’m actually working on one of our exciting new projects, which is looking at measurable residual disease in heme cancers, and particularly, we are looking at AML, which is one of the most challenging heme cancers to look for MRD in. I’m very excited about that project because I think that Mission Bio Tapestri technology has an incredible set of benefits that bring another level of prognostic value to monitoring for MRD.

Ania: Tell us a little bit about why MRD – why is this even worth looking at?

Nicole: A lot of times, when people are treated for a cancer, they may be treated with an immunotherapy depending on how their cancer has progressed, but a lot of times, they’re just treated with chemo and radiation, and then they go into a remission phase. From there, it’s really unknown whether or not the patient is going to have a recurrence of the cancer. In particular, AML has a pretty high recurrence rate as well as the fact that it’s a very difficult cancer to detect MRD in because it’s very heterogeneous and can actually change genotypically pretty wildly from the point of diagnosis, all the way through to a recurrence.

So, patients, once they’re considered in remission, are actually recommended for the next two years to be monitored at three-month intervals for MRD. We feel like that’s a great opportunity for us to not only bring the power of our technology to that monitoring phase, but it’s also a great market opportunity for us in terms of the number of patient tests. So, that’s about 24 patient tests that would be available to us over a two-year period.

Ania: You mentioned that most patients get MRD testing done currently. How is that done today?

Nicole: Currently, there’s a couple of methods out there that are considered the “traditional” methods. One is multicolor flow cytometry, which is a method that’s actually been around since the 1970s. It’s a well-established method, and it does a nice job of being able to identify cancer cells and populations of cancer cells, but it really doesn’t get down to that level of specificity that you would see with a single-cell technology like Tapestri.

Sometimes, if patients have known mutations, they’re actually monitored using PCR methods, which are highly sensitive, but you’re really missing that immunophenotype information that you can get from the Tapestri Platform where you’re combining multi-omics to get a DNA + protein profile. So, really, those two methods kind of give you one piece of the puzzle, and Tapestri brings both pieces together for a multi-omics approach.

Ania: That’s fantastic. Can you tell us a little bit about how Tapestri is going to work for this type of assay?

Nicole: We use a multi-omic approach, which combines the DNA profile information as well as the protein profile information for the MRD patient, and that would be done by taking a bone marrow sample from the patient, enriching it, enriching the cells using a e-based approach, and then it would be run on the single-cell Tapestri platform to be able to get a very specific level of information around what types of variants or mutations are present in the cancer cells that are found. That information can be used to detect whether or not there is a recurrence of cancer.

So, it looks at a very finite level for MRD. It’s almost like looking at a needle in a haystack because if you can find a single cell with a change in a large population of bone marrow cells that are mostly healthy, meaning you would be able to find the cancer early, then you have a much better chance of being able to put a directed therapeutic toward that patient early on to prevent full disease reoccurrence.

Ania: Since this product is still in the initial development phase, you may not be able to speak to too much of it, but what kind of results are you getting with this approach?

Nicole: We’ve done some feasibility studies, and we also have some collaborators that have been running our assay for AML MRD, and we’re seeing a specificity down to, in the range of 0.01% with known mutations. Yeah, with known mutations, with de novo mutations. It’s a little less sensitive because we don’t know exactly what we’re looking for, but we are seeing a very good specificity there as well.

Ania: So, break it down in kind of more real terms. How does that factor in? That would be one in 10,000 cells? Is that right?

Nicole: Yeah, about one in 10,000 cells is what we’re seeing right now.

Ania: That’s fantastic, and how does that measure up to the current standard of care?

Nicole: So, while it’s a little bit less sensitive than a PCR assay, as I mentioned before, you are getting that added layer of immunophenotype information, which can really help you get a deeper level of understanding of what’s going on with the MRD, and it’s on parity, a little bit more sensitive than flow cytometry, but again, flow does not give you that genotypic data. It’s really looking at that combined power of being able to look for the genetic changes as well as the phenotype changes.

For example, if you think about a cancer cell, it can evade detection actually by changing, by creating mutations and changing how it’s detected. So if you don’t have a technology that’s sensitive enough to look for those very finite mutations and genetic changes, then you can potentially miss it and have a false negative and say somebody is fine and clear, but they might actually be starting on the path to having a cancer recurrence.

Ania: We don’t know what we don’t know, and so if you don’t know it’s there, how can you do something about it? I think cancer diagnosis, it’s always been that name of the game of detection as we’re trying to detect it earlier and earlier to make those clinical decisions, so this is really fantastic. Can you talk a little bit about your background? You’ve had a lot of experience at other genomics places that have done similar testing for different reasons. Can you give us a little bit of sense of your background?

Nicole: I actually started off my career many years ago, working on the Human Genome Project at Applied Biosystems. That was my first job as a scientist and worked in infectious disease and some other areas, spent some time a number of years working on the early parts of The Genome Project, as well as other technologies that kicked off from there, including Affymetrix, where we were looking at microarrays, and how those impacted eventually clinical care. So, it’s actually been really exciting for me to see all these genomic technologies that I worked on and even working on the very basic DNA sequence, seeing that come to therapies and clinical products now here in the future.

Additionally, I spent a number of years at BD Biosciences where I managed our clinical instrument portfolio – I actually was working on instruments and assays for clinical flow cytometry. I feel like I’m really blessed to have that kind of that mixed background of being on the genomic side for a long time, the cell analysis side, and then now to see them all come together in these single-cell technologies is really pretty incredible and then seeing those move toward the clinic in order to eventually impact patient care, improve patient care, and eventually one day maybe curing cancer. Also on the pharmaceutical side, these technologies are going to be very valuable in drug discovery, in discovering new therapeutic targets and really understanding why one patient responds to a drug and the other one doesn’t through clinical trials.

So, that’s actually another thing I didn’t mention previously is the pharmaceutical use of our MRD assay. So, with flow right now, flow actually requires fresh bone marrow. Our assay can use cryopreserved or fresh, which means if you’re doing drug discovery and you want to do a retrospective trial, our technology plays in nicely with that, giving you that extra layer of information and also being able to be used on bank samples as well.

Ania: There’s a lot of issues with access to healthcare in remote places where they may not have a hub to be able to do fresh samples on the spot. I imagine once this technology is proven and can be used more widely clinically, the ability to freeze them and transport them would also be incredibly valuable.

Nicole: Yeah, absolutely. It’s very difficult to get a fresh bone marrow. Usually, the sample is preserved so that they can be sent for testing, so it is important that you have a sample type that can be readily supported across the modalities that you’re looking to support.

Ania: I was just reading an article this morning about the Illumina acquisition of GRAIL and the FTC filing, defending them because they’re getting sued by the FTC to stop the acquisition. They mentioned all these competitors that are coming up on the sequencing landscape and some new ones that are now promising $100 genomes, which I think they cited whole genome being a couple of billion dollars was the cost of the whole genome project initially in 2001.

Nicole: Ha, yes.

Ania: It’s pretty amazing the cost of sequencing going down and really, the accessibility in a clinical setting. So, I do think that, exactly what you were saying, this technology is kind of having another revival almost, and the inexpensiveness is going to help lower those clinical hurdles and make it even more predominant.

Nicole: Yeah. Spending, when I think back to 1994, 1995 when I was working on The Human Genome Project, it was a collaboration with the NIH and Applied Biosystems, and so it wasn’t Celera. It wasn’t the TIGR, Craig Venter thing yet. We had predicted it was probably going to take us about 30 years to finish the genome. And we were only doing one genome.

Ania: Wow.

Nicole: One person. I remember doing the sequencing runs during the day, which were fairly fast, but you were going well-by-well, and then we would put the data in the computer and go home. You’d wake up in the morning, and your assembly would be complete. So, it would take overnight for a genome to be assembled.

It’s not just the sequencing technologies, but it’s also the bioinformatics capabilities, and that’s another thing that Tapestri is going to bring to the table with our MRD solution. We are going to have a bioinformatics solution that will allow for users who may not be as savvy in bioinformatics or they don’t have that bioinformatics support within their institution. They will have a way to take their data all the way to a report that says present or absent for MRD all the way with a push of a button within their software. Bioinformatics cannot be underestimated in all of this.

Ania: Absolutely. It’s so much data that you can potentially generate, and making sense of that is a huge hurdle. So, I’m really glad that’s part of the pipeline here for this solution. Talking about big picture things, what do you see as the future for both the clinical utility in this case as well as Tapestri use?

Nicole: The MRD market is a $1.6 billion market. That’s the estimate through 2025, and it’s got a pretty high growth rate and about 15% is the CAGR that we’re expecting. So, there was a huge opportunity to bring in a game-changing technology and be able to take a big piece of that testing market and make it successful. At the end of the day, we’re interested in making oncologists and people trying to treat patients and prevent recurrence of cancer successful, and so there’s a great opportunity for us to do that.

Because of our technology being so flexible, and really, what we’re talking about here is rare cell detection, I see us moving into many different heme cancers. There’s multiple myeloma. There’s ALL. There’s all sorts of heme cancers that need monitoring for MRD, so those are kind of the obvious next targets, but you can also start to think about using this technology for things like CHIP.

Ania: For people who don’t know, what is CHIP?

Nicole: CHIP stands for clonal hematopoiesis of indeterminate potential. Basically, when people age, you get more and more mutations, which is why you see AML in older patients, because your cells are dividing over and over, so there’s a higher chance for mutations to come in. With CHIP, they actually think there might be some use for looking for cardiovascular markers and things like that, so being able to pull these rare cells out of blood and being able to understand them at a genetic level and also be able to marry in the phenotypical information is going to really be powerful for future clinical applications.

Ania: I know we’re going to discuss this with Aaron Llanso who’s my next guest on this podcast series, but can you speak a little bit about what this means for patients? How would this impact their care?

Nicole: So, in terms of impacting patient care, what you’re talking about is somebody who’s going in for monitoring already over a period of a couple years that’s required for them to make sure that they’re definitely cancer-free, and really it gives them a sense of security that when they get a result that said you’re not having an MRD situation, you’re not relapsing and knowing that the false negative rate is very low on the technology that’s being used to diagnose.  That is really important because you’re missing the MRD and finding out that a patient reoccurred even after you tried to monitor for it can be devastating to the patient. So, you have to remember the emotional aspect of all of this.

This is a person that has survived cancer. They want to move forward with their life, and they’re probably afraid that it’s going to come back. Making sure that they have the best quality answers with the most confidence in them from their oncologist will really have a huge emotional and health impact on patient care.

Ania: Yes, because we know the sooner we know something, the better we can monitor it, the better we can treat it. Because this does give you genetic information, presumably, once we have a better understanding, we can then also work out what treatments these patients might be able to get in a better, more succinct manner.

Nicole: Yeah, absolutely. So, when you look at the pharmaceutical aspect of it, pharma companies using MRD monitoring to look at their clinical trial success and which patients have done well and which haven’t in terms of drug therapies, they could start to really refine and do patient stratification based on that. They can also start to develop more targeted drugs for particular mutations that might happen within the population that weren’t known before. So, it does bring this added level of care and therapy selection for patients overall.

Ania: So, just to wrap up, we talked about very long-term goals, but what is near term? What’s happening in your world?

Nicole: So, in the near term, we just launched an Early Access program for MRD. Institutions that would like to have us help them process samples for a proof of concept study, so in order to kind of demonstrate clinical utility in their own lab, we are available for discussions around that. We are going to be launching a full product sometime in 2023, and so that will be an option for labs that want to bring MRD testing with the Tapestri system in-house.

Ania: Yeah, absolutely. So, one very obscure question, maybe a bit of off-topic but something that I really like hearing about is you’ve made a lot of career changes, transitions. You’ve been very successful in what you’ve done. What’s the best advice that you can give for listeners who are looking to have a successful career in life sciences?

Nicole: Follow your passion is really what I say. I mean, there’s the famous Steve Jobs speech at Stanford about you really have to love what you do in order to be successful, so that’s part of it. I’ve always loved science, and being a single mom for most of my career, it’s been a challenge for me to keep my forward momentum because a lot of times, family obligations were pulling me in different directions. So, I did, at times, kind of take the gas off a little bit and find sideways to that weren’t as high pressure that allowed me to be with my family more to keep my interest level high in what I was doing, as well as move my career forward. That’s actually the reason why I got into clinical.

My daughter was born with a heart condition, and I really got an awareness of health impacts on individuals through that time when she was little. That’s why I ended up at BD because I wanted to learn the clinical market, and then losing a lot of friends and colleagues to breast cancer over the years has really made me want to stick it out and help scientists and researchers who are searching for better therapies, better outcomes, and potentially cures for the many types of cancers that are out there. So, my advice would be just follow what interests you, what keeps you motivated. Don’t let yourself become stagnant in a boring job just because you have security. Sometimes, you have to take a little bit of a risk.

Ania: That’s a really, really great advice. I really appreciate it. Thank you. Then, one last question – what is your favorite ice cream flavor?

Nicole: Ooh. I would have to say mint chocolate chip. Yep.

Ania: That’s a good one! Well, thank you so much, Nicole. I really appreciate your time, and thank you so much for giving us such an incredible insight into that MRD or measurable residual disease product that we should see very soon.


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