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NanoString: Digital Molecular Barcoding Tech for Oncology (Interview)

December 2nd, 2015 Thomas Obisesan Exclusive, Genetics, Oncology, Pathology

nCounterNanoString is a biomedical company that is first to class with their digital molecular barcoding technology. NanoString develops devices that analyze multiple analyte types simultaneously from one sample of tissue. That means that in the same tube a researcher can study a pathway through a multiplexed approach, capturing mRNA, DNA, and protein expression. This is all made possible through their 3D Biology approach. The company’s flagship device, the nCounter Analysis System has the capability to analyze up to 800 different targets in a single reaction, opening the door to a more streamlined approach to pathway research. Noticing the need for their technology in the field of oncology, NanoString is now tackling the complexities of cancer immune responses and the development of predictive biomarkers. In their breast cancer genomic assay, Prosigna, they address these issues while developing companion diagnostics for clinical settings. While presenting their new product, the PanCancer Pathways Panel, at the annual SITC conference we had a chance to sit down and speak with folks from NanoString about their move into oncology and what their technology means for the field.

Thomas Obisesan, Medgadget: What got you involved with Nanostring?

Joseph Beechem: I was a professor, and I did that for about 11 years, and from what I could tell science was changing in the sense that what you can accomplish at the academic setting in science, when you wanted to push something to all the way to a patient level, was really pretty limited. So I decided I need to go out of academia and into something where I can make things that are useful. I left academics and went to a small biotech company out in Eugene Oregon called Molecular Probes. They make a whole bunch of imagining reagents, a nice biotech startup that was going to go IPO before we got bought by Invitrogen. Then I worked at a bigger biotech company, and that was up to about 3 ½ years ago.  Same thing there I worked on next-gen sequencing, but I realized something was missing. There were some things you just couldn’t measure well with just pure sequencing approaches. I needed to find another way to do this. There were things I didn’t want to give up, the total imaging data really makes a difference.   So I was looking for other technologies that could be more broadly based like proteins and doing all sorts of those things together in a single tube. So when I looked around I found the optical barcoding technique which is what the NanoString technology is. I realized I could use optical barcodes to count all sorts of different types of analytes and put together this sort of 3D biology vision, and that’s the path that brought me over to NanoString.

Brad Gray: My backdrop story is that I joined Nanostring five years ago from the clinical lab industry. I ran product development and business development for a part of Lab Corp. My own R&D team wanted to bring technology into the lab to build these multi-gene cancer assays. The conversation turned,  Nanostrings board was thinking about entering diagnostics at the same time. so I went and joined the company. Really the vision was to take a technology that is already gaining a strong following in research through the FDA so we could decentralize the kind of cancer test you heard Merck and Cellgen talking about  in our session. That has really been a big goal, for the last five years, in addition to building out the research capabilities, we’ve been really trying to figure out how to take things directly to the client.

Louis Welebob: My name is Louis Welebob. I head the global marketing group at Nanostring. I came out of the pharmaceuticals industry working with small molecules and vaccines, and progressed to technologies. I worked extensively with microarrays and mass spectrometry before coming to Nanostring. Immediately prior to coming to Nanostring I worked for Merck diagnostics.

Medgadget: So the goal is to move the research to actual clinical application?

Brad Gray: That’s right, and so our most popular system today is a system called Flex, that is actually FDA cleared to run our first diagnostic assay, a breast cancer assay, and it does everything that the researchers only product can do. So a lab in a cancer center could buy one system and do their discovery and later use it in the diagnostic mode.

Medgadget: So what led to the move to apply this optical barcoding technology to a dedicated oncology platform?

Brad Gray: Our first wave of customers happened to include some cancer researchers, and actually the breast cancer assay that we’ve taken to the FDA called Prosigna came from our third ever customer. So very early on after we put the product out on the research market the cancer community embraced it. The reason they did was because cancer biology is the place where the problem of too little tissue and too much biology you want to extract from that tissue is being felt most acutely, and it is compounded by the problem that tissue is stored in formalin  fixed paraphynetic tissue, basically mummified, which makes it really hard for other technologies to work with it, but our technology works great. So very early the cancer community felt, look at all the genetic information I can get out of this little biopsy I have with this really efficient platform. So we felt that and saw that trend, and then ultimately we decided that this was a cancer company. Our technology can do tremendously good things in cancer research and diagnostics, and now that has become the organizing theme of our company. Almost all of our product development efforts are around how we can better with cancer.

Medgadget: How has the system evolved since conception?

Nanostring-nCounter-SPRINTBrad Gray: Joe has been working on making it more affordable with the nCounter Sprint System, built for the individual researcher.

Joe Beechem: We made a little personal computer sized version of this instrument that is pretty expensive and two big boxes  and we took one box and turned it into a microfluidic card that sits inside our other system, and it is a unified system that costs $149,000, making it more affordable for the individual research to have their own system.

Brad Gray: That is one big thing, and the other big thing is what we call 3D Biology.

Joe Beechem: When we got pulled into cancer we wanted to help pull the cancer technology forward, and one of the big things was that the individual technologies were not very good at crossing boundaries of the analyte types. It was total different instrumentation to do protein work versus nucleic acid work. In reality you need those two things talking to each other well, especially in immuno oncology. This is an area of cancer research this is exploding, almost like a revolution no one has ever seen before. Then the other thing is that we think this 3D biology approach is ideally suited for immuno oncology. You have to be able to pick pieces of information from the DNA level, the protein level, and the mRNA level and put them all together to make a really informed decision. I think that is why I am really excited about this 3D biology approach, and you saw the data, the data is just gorgeous, you won’t see correlated data sets like that anywhere else.

Medgadget: What was your favorite research that has applied Nanostring technology thus far?

Joe Beechem: If you’re going to integrate it all over, I think we all have our our individual favorites.

Brad Gray: It’s like asking who is your favorite child.

Joe Beechem: You know, I really like these researchers who believe in pathways, understand pathway based approaches, and do quantitative pathway based work. There is a researcher up at the Broad that I really admire a lot, and her name is Aviv Regev. Aviv is a woman, and she does great pathway-dependent biology, using our technology to basically understand the mechanism of how mammalian cells actually make mRNA, how they regulate it, how long it lives, how it gets utilized in a pathway based manner. She has done a great job on working with our technology

Brad Gray: Good basic science. My favorites are probably more applied, the Blood paper that came out in January 2014 that showed a set of researchers hat really had no idea how to really build clinical diagnostic assays . I mean that is not what they do for a living. They took our technology and built ideal BCL tests. The test that we use with Cellgen, they developed that, and they developed it so well that when we  brought it in we didn’t change it. To know that our technology was so simple and powerful that a set of researchers could themselves build a diagnostic, that was the best in the world at subtyping that disease. They actually did something pretty sophisticated called a multi-side analytical validation where they ran it in three different labs and showed that they got the same results. That is the kind of study you do for the FDA, nobody in research does those kinds of studies and gets good results. That was one of my favorites because it just shows how simple and robust the technology is.

Louis Welebob: My favorite was really what we did to bring Prosigna to the market for  the diagnostic. What I saw was as people struggled to build the signature, the signature that essentially became Prosigna. What I saw was them move by a leap in accuracy, reliability, and reproducibility when it became part of the Nanostring family. I saw the data, the clinical trials, and everything else, so when Joe talks about the data also go and look at the Prosigna trial data. You never see anything else that has ever been done so well on Paraffin embedded tissue, in the breast cancer space, and the gene expression signature. It is the tightest data set you will ever see. So from my perspective , today as Prosigna is on the market and now we’re seeing oncologist really take advantage of that test, they are coming because  what it’s doing and what it’s giving to them they haven’t really been able to get so far. So the way that the technology that Joe developed is now applying itself to helping the breast cancer patients is really in my opinion one of the most profound things that has happened in medicine in the last 10 years.

Medgadget: Any insight into future R&D and the direction of the company?

Joe Beechem: This 3D Biology approach, we are first in class in that space. They call that blue ocean area, a space where no one has ever been before. We are taking that really powerful technology, and you can see how closely we’re partnering with people who are doing this really cutting edge oncology research and immuno-based therapies. You’re going to see us take that thing as far into immuno oncology as we can possibly go. I think that it is really changing cancer treatment and diagnosis. I can’t believe how big a change it is. I think we are seeing the last generation of people that will die from cancer. Your generation or next, you’ll  die from something else, but hopefully it won’t be cancer. It will be great to put that thing to rest and we have a real path for it now. Our role is to help accelerate the development of the cure for cancer. It is a very exciting place to be in.

Brad Gray: Most companies that are technology companies, as ours was originally, don’t ever make statements like that. They don’t focus on a particular disease area, or they don’t view their mission as going any further downstream than providing the tools for somebody else to use to fight disease. I think that is one thing that is really different about Nanostring, that we are really proud of. if you went around and asked our employees why they get out of bed in the morning, a majority of them would tell you it’s because of the clinic. Even though I’m selling the basic research, I’m building technology, building blocks. I’m here because I know we’re going to take it all the way.

Louis Welebob: The market is demanding better test better technology working from a single sample and maximizing the data out of that, being able to really not just get a data point  but make it interpretative. I believe this is what we’re doing. When you start thinking about it 3D biology adds additional context to your data points, giving you multiple pieces of information coming out of one sample, coming together at one time. Adding additional context to that really makes the research go faster. So that is what you’re seeing now, the advent of something that is really special. We are resetting the rules right now with the 3D biology technology.

More info: NanoString…

Thomas Obisesan

Thomas is a graduate from Howard University, with a passion for medicine, technology, and innovation. He has worked in numerous labs including the Georgetown Neuroscience and Psychology Lab, The Veterans Association Medical Center, as well as the Neuroscience lab at his alma mater, Howard University. Thomas has earned a B.S. In biology from Howard University, and is pursuing his MD/PhD. Have any burning questions, or technology you want to see covered? Feel free to get in touch with him. Happy Reading.

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