Former VP, Biology
Former VP, Biology at CyVek
This executive has a background in nucleic acid amplification, next-generation DNA sequencing, microfluidics, genetics, molecular biology and product development, with experience in innovative technology development from the initial start-up to product launch stage. He is currently the SVP R&D at IsoPlexis, and previously held senior roles 4Catalyzer and Quantum-Si and Qiagen among others. At Qiagen he was Head of the global Next Generation Sequencing (NGS) development team, responsible for management of the technology development driving QIAGEN’s NGS GeneReader system. Read moreView Profile Page
Disclaimer: This interview is for informational purposes only and should not be relied upon as a basis for investment decisions. In Practise is an independent publisher and all opinions expressed by guests are solely their own opinions and do not reflect the opinion of In Practise.
I have a friend who does clinical research and he was very helpful getting the basic lexicon under my belt to browse through this space. I found Abcam interesting because it's one of those companies where when you speak to a generalist, they're like, the science is really challenging. But when you speak to a specialist, they're like, these guys talk about their catalog and their SEO too much. I view them a little like Amazon insofar as they started by taking something analogue, making it digital and then verticalizing by getting the actual capability. That was kind of like my basic entry into the space and I'm still trying to make sure I truly like and understand the situation as much as I should.
I followed Dr. Rothberg back in the day because Ion Torrent was incredibly fascinating to me. Early in our history as an investment company, we had a position in Life Technologies. I followed Ion Torrent through to the acquisition in Thermo. I understand you all are working on some very interesting stuff nowadays as well. I’d love to hear about your background, your history personally, your history with Dr. Rothberg and then go from there.
I got into biotech right out of my post-doc and the driver for me was realizing that I enjoyed the interplay between biology and the technology itself, so putting biology into boxes was what I joked about. I actually started with Jonathan at 454 in 2000. That was just really getting my feet wet and designing some of the key components of that system. It was a fantastic group and the perfect time to join; before anyone knew what next gen sequencing was.
Then we sold that to Roche. I went over to RainDance Technologies which was droplet based, one of these kind of microfluidic companies. From there, I went to Ion and rode that through the sale to Life Tech and then stepped out right before the Thermo acquisition. I went to a company called CyVek which was up in Wallingford, Connecticut and had a little desktop biomarker discovery unit that was antibody based. This was really my first foray into the dark side of proteins instead of DNA.
That’s where much of my antibody experience that I can talk about directly comes from. There we were creating an instrument that also had a consumable chip and that chip allowed for highly multiplexed, low sample volume analysis for antigens, whereas with companies like Luminex we have a whole mess of beads and each one of these beads captures a different analyte. So you can have a mixed population of beads and some are detecting Interleukin-8 and some nine and some six and some TNF-α, and you throw them all into a pot and they're all individually barcoded but there's also, cross-reactivity that occurs between these antibodies. There's always some level of non-specific binding.
That causes a loss of sensitivity in general, but obviously not so badly that the technology doesn't work. People use it by the bucket. The CyVek system had these parallel paths and you would put one sample in and then it would get routed through these parallel fluidic channels. In each channel there were specific antibodies that you would be testing for an antigen, so you could test each antigen independently but you used a very small amount of sample which was important for things that were biologically relevant. That's where I first came into contact with how do you screen for antibodies? How do you select the antibodies that you're going to use in these systems? Who do you get the antibodies from; all of this kind of stuff and the scalability of that aspect?
We then sold to R&D Systems. I was part R&D for a little while but really it didn't make any sense for me to be trying to teach R&D Systems how to do antibodies. They had people who had far more experience than I. Then Qiagen hired me to lead the GeneReader launch program there. That was the next three years which was running the system and then taking over the site administration and being the site lead, then came back to work with Jonathan again because it's a fascinating experience.
So at this point, he was no longer doing just single companies. He now had the incubator, the 4C incubator and so I think at last count he's got seven or eight companies that are under direct management there. I came in to work for Quantum-Si. COVID hit and I left Quantum-Si to work for Detect because it seemed timely and we needed to build up a group. We went from no people to a company of 150 people with an at-home COVID detect kit that is currently under EUA testing right now. That was a fun project but then IsoPlexis called and really gave me an offer that just was too good to pass up, so jumped over there.
Very interesting. You’ve been involved from the nascency of working with DNA and then down into the proteomics level and into next gen, so everything.
I've been so lucky; what an amazing time. I was able to get into next gen when it was first starting and now, I really feel that I'm in proteomics at almost exactly the same stage. With quantum, coming up with a protein sequencing, that was just an amazing kind of application that really dropped. It wasn't the intended application for the company at all initially. We were looking at long read DNA sequencing and then the ability to do protein sequencing came up and that was a total greenfield. Nobody can do that and so that was a very reminiscent pivot. It's been so much fun. I don't stay long. Usually it's about three years or so and then it's time to go find some other challenge, but the opportunities have been so entertaining. It's just been an amazing run.
Could we dive into first your experience at CyVek where you were actually purchasing the antibodies and involved with specific antibody tests. Given you sold to R&D Systems, they may have been your primary vendor?
It's interesting. There was a perception of a hierarchy. In R&D you were going to pay top dollar, but you were going to get quality. That was the top tier antibody as far as reproducibility and quality, but you were going to pay through the nose for it; frankly, you pay through the nose for all antibodies. The bottle that you get the antibody in is infinitely more expensive than the antibody itself. The margin on this thing is insane. It's biblical. It’s a great market to invest in. Having learned what I've learned, it's just kind of eye-popping. I used to think that polymerases and stuff were a crazy markup, but antibodies are just insane.
For R&D Systems, we used a lot of them, but Abcam was a very strong runner for cell signaling and CST; they were also quality. What would drive it would be trying to find who made antibodies for your specific antigen of interest; it was a very strange system of testing where you never knew what antibody was actually going to be the best for the antigen that you were using. You would order antigens from everybody, whoever had it, and you'd bring them in and you'd do a variety of either ELISA testing or whatever, look at the sensitivity, look at how well it worked in whatever buffer you were using which might shift.
If you were multiplexing, it suddenly became an added layer that not only did that antibody have to work well in a given buffer, but it had to work well enough in conjunction with these other antibodies because you might have to find a buffer that they all worked well in, but none of them were at their 100%. There was very much a kind of horse trading. Then you would want to change a panel. I’ve got a panel that's got five antibodies, six antibodies in it and somebody wants to replace one for another. You might have to reoptimize everything and you might need to move out, replace some of your antibodies with different vendors’ antibodies because that new antibody that you've added is really particular about what buffer it needs.
I expected it to be a lot more predictable coming from the DNA world. In the DNA world, there are rules, dammit. You can make TCR primers or whatever and they just work. But there's really this empirical settling on what will work best and it's very fluid.
We used a lot of R&D, but also we’d use Abcam. You’d order a lot of them; you’d test them and sometimes you would be forced to only go to one specific vendor because they were the only people who made that antibody for that specific antigen that you're looking for. So you might have to go to some of the Chinese vendors or Santa Cruz Biosystems where everybody winces.
I’ve heard their alternate name.
Yes, so you're familiar. Let’s just be kind and say that there's a wide range of expected quality that you may get. Then there's the second wrestling match that you need to do which is when you are looking at a commercial product, it's not enough to simply get the antibody that works. If you're writing a research paper or whatever, can get a golden tube of antibody that works and that's great. That's all you need. But we were looking at being able to lock in long-term supplies and, in that case, you've got this interesting dynamic between the monoclonal antibodies which are the same antibody tube after tube after tube. They're either recombinants which are the ideal ones, so you get the recombinant monoclonals, so a different lot should perform exactly like the previous lots. Once you've got this one dialed in, it comes in.
That's not the case for your polyclonals. If you get a polyclonal and you inject something into a goat or a sheep or a rat or whatever and then do a bleed and pull out the stuff, rather than one specific antibody that binds to one specific spot on the antigen, you get a whole variety of antibodies that the goats produce. In many ways it's a much better solution because you're going to cover that antibody eight ways from Sunday. But once that batches out, they have to bleed the goat again. They have to stick the antigen back into the goat and, in all likelihood, you're going to get a wildly different bunch of polyclonal antibodies and so you're going to have to redo this whole titration again because things have changed dramatically. Those are the kinds of questions that you would go through as you were looking at different vendors’ offerings.