Meet CRISPR QC

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Value Proposition

CRISPR QC is the first CRISPR Analytics Platform that can simulate gene editing under a wide variety of conditions. They provide innovative quality control metrics and insightful data to enable revolutionary advancements in therapeutic medicine and sustainable agriculture.

Ross Bundy

Ross Bundy

Founder & CEO

About

CRISPR QC’s CRISPR Analytics Platform provides comprehensive measurements and analysis around CRISPR activity, enabling scientists and researchers to optimize gene editing outcomes and ensure the highest levels of quality control. The platform is built on the company’s proprietary CRISPR-Chip technology, which allows for direct, real-time measurement of CRISPR activity.

Why We Invested

We believe that gene editing, particularly CRISPR CAS9, will play a large part in the future of personalized medicine. This technology is currently prohibitively expensive and time consuming. CRISPR QC’s platform will change that. We believe that Ross & his team have the right experience and are positioned to succeed.

Highlights

CRISPR QC has negotiated an exclusive license to the CRISPR-Chip from Cardea Bio for gene editing applications. In addition, they have established a relationship with NIST— utilizing the CRISPRQC platform will likely become the standard in gene editing procedures.

ela chi abruzzo, john shufeldt, anuncia, anuncia medical, entrepreneur rx

About the Episode:

Our GP, John Shufeldt, interviews Ross Bundy, CEO of CRISPR QC for episode 83 of Entrepreneur Rx. CRISPR QC is a biotechnology company aimed to equip scientists and researchers with data to improve their CRISPR assay design by using its sensor technology to analyze gene editing processes.  

Ross starts off the episode by discussing his background in gene therapy and his experience founding Cardea Bio. He also talks about the challenges of introducing new ideas in a field dominated by experts and the importance of regulatory guidance. He goes on to explain more about how Cardea Bio and CRISPR QC are related, ethical issues in the field, challenges gene editing faces and his excitement of where CRISPR QC is headed. 

He concludes the podcast by emphasizing the importance of building a strong team and finding people’s strengths to create a successful startup.He also shares his advice for those considering starting their own startup: build a support network, learn how to translate their expertise into value, and take responsibility for supporting and leading others. 

Ross Bundy.mp3: Audio automatically transcribed by Sonix

Ross Bundy.mp3: this mp3 audio file was automatically transcribed by Sonix with the best speech-to-text algorithms. This transcript may contain errors.

John Shufeldt:
Hello everybody, and welcome to another edition of entrepreneur, where we help health care professionals own their future. Welcome back to another episode of entrepreneur. I'm your host, John Shufelt. Today I'm excited to have a chance to talk to Ross Bundy. He's an interesting guy because undergrad degree was in Chinese history, believe it or not. He went on to get an MBA and then started going down the entrepreneurial path and has a couple of startups under his belt. Ross is the CEO of a company we invested in called Crispr QC, which is really on the forefront of gene therapy. He was also the co founder and chief entrepreneur of a company called Cardea where Crispr QC spun out of. And so it'll be really cool and exciting discussion. Ross welcome to the show. It's good to have you on it.

Ross Bundy:
Thanks, John. Good to be here.

John Shufeldt:
All right, Ross, you've done a lot of cool things in your life and a lot of really cool startups, but let's back it up because people are going to want to learn how you got here, like what the origin story is.

Ross Bundy:
So I have a very strange background, and I'll admit, I was reading one of your posts on LinkedIn and just resonating with that too, because while I'm in life science, I don't come from life science. I don't even come from health care. I started my college degree with a background in history. I ended up getting a degree in Chinese history, working in finance for a while and then moving from there into defense manufacturing. So I built ships for many years, but I learned Lean Six Sigma. I learned how to build complex supply chains, how to manage a lot of different projects, did some business development with some with our shops in Mexico, and finding new jobs outside of the shipbuilding world, then transitioned into consumer packaged goods again, doing something very simple, just tuna in a can, but very long complex supply chains. Interesting dynamics about how to manage demand with unknown inputs, unknown outputs, you know, and building that control systems all the way through. And as I was finishing my MBA, I was stepping a little bit into venture capital entrepreneurism. There was a couple of different opportunities that I had to really explore. What does that mean as being part of a VC and getting to know some VCs and said, you know, I could do this. This sounds it's not quite as scary as it might seem. Maybe I could give this a go. And I've been fortunate in my life to have a number of different, very close connections who went very different paths, and then finding that ability to merge these two skill sets together.

Ross Bundy:
So an old friend of mine from high school did his undergrad the physics route and put together this technology was weaving his whole point in his career, saying, hey, I want to do a startup and said, I kind of want to do a startup, and I've got more business sense, and he's got the technical sense, so let's pull this together and get going. And that was the beginnings of Cardia in 2013, our first company, which we built for many years. I ran it for about six years, recruited a new CEO as we transferred into a new commercial model that didn't feel I had the skill sets for, so I went and found a guy who had those skill sets, and he grew the company from there. And then we started seeing opportunities and setting up applications. One of the co-founders we brought in as we merged companies with another CEO, Dr. Kiana Ron. She and I got to know each other really well, and she was the inventor of combining our sensor at Cardia, but with Crispr. And we said, hey, we can do a lot in gene editing. Let's build an application of this and let's go out and do that. And so I've just found a way to use very different skill sets from very different industries and mix that together and then just build a good connection with people that are really experts in their field and see how do we put those skill sets together and build something new. And that's where it came from.

John Shufeldt:
So the book I just finished is called Seeing What Others Don't. And what you just described is basically the book. It's this parrot bits of information, and you're able to weave them together and people along with it and come up with a business model and plan and execute it, which is very cool. I think it's a rare skill set. And I think part of the reason it's rare is because not a lot of people, pardon the expression, have the guts to do it because you are way outside of your lane. I mean, come on, you were a history major.

Ross Bundy:
Yeah, yeah. You know, I think there is a story in startups that is that scientist professor who leaves their academic work to go build a company. And there's been a number of those stories that people kind of advocate for. But the reality is that building a company has a lot more to do with people skills. Building a team and technical people often don't want to leave their technical field. But I've told many scientists that I know who want to reach out and be an entrepreneur, okay, if you're going to be the CEO, you're not the technical person anymore. You can't do that. You got to hire someone else to do that because your job is something else. It's about making sure everybody understands what they need to do. Building organizations I often tell people in my MBA, one of the most boring classes I took was organizational development. And then I started building a company and realized it was the only class that mattered, was building an organization that leveraged people's strengths and made some of those greater than the sum of its parts. And so, to some degree, all the different things I did has taught me about a lot of different types of people. And really all I do is, I like to say as an entrepreneur, I can do everything the company needs. I'm just bad at all of it. I'm like, maybe a two or a three and sometimes that's all you need for a company. So, okay, I'll take care of that. And then the company grows and I'm like, now I need a five. So now it's time to hire an eight. And how do I build a structure for that eight to be successful at that skill set and grow with a company, and we hand off those responsibilities, and then we just keep handing off little bits and pieces as the company grows to people who are experts in those verticals and then just fit them together and organize it.

Ross Bundy:
So really, leadership is not a technical field. It's more of an empathic field. And much of my skill set, turns out, was pretty good at that. And that's been how I've done everything I've done. I learned science from the best scientists. I try to regurgitate what they say. I listen and then try to put in my own words to make sure I fully understand it, and I can talk it as best as the next ones. But I think in some ways it's also given me a little bit of an advantage in a highly technical field. I often say one of my greatest strengths is that I don't have a PhD, which means I can come in and say, I don't know what you're talking about. I could be the stupid guy in the room. Bring it down to my level. Explain it at the most basic level, because sometimes people get lost and they don't want to say, well, I don't really know what you're saying, but have all the power to say that because I don't. And then people explain it, and then we start fitting these pieces together. As a result, it's allowed me to take on the responsibilities that these really brilliant technical people that I work with can do their job, and then I can take the other pieces and help shape that into something.

John Shufeldt:
Yeah, I think a lot of people, and I've made this mistake or starting the business, tend to gravitate to people who are like them. You know, for example, emergency medicine physician, let's go find another emergency medicine physician to start a business with, which is great. But if you both have the same exact skill set, as Henry Ford said, if there's two of you at the table who know the exact same thing and think like one of you is not necessary, so the fact that you're able to figure out I laughed when you said, I'm a two and everything. I describe myself that way too. I'm an inch deep and a mile wide, but the fact that you're able to a were attuned enough to realize that about yourself and then have the skill set to bring other people in is really an unusual trait.

Ross Bundy:
You know, think I've never found someone exactly like me. I've always been in multiple groups and kind of an outsider. So I use this example. Even when I was in high school, I was in classes, but I was never the top of those classes. I was usually, you know, in the, in the B or below range, you know, so I was doing okay. But I was also one of the first varsity athletes in my class in high school as a varsity athlete in swimming my freshman year. So I was always the smart guy with the jocks, and I was always the jock with the smart kids. But I was never one in any group. I was always a little bit in multiple groups, and I still find myself being that way in a lot of ways. I spend a lot of time with very educated people, very successful people. When I'm not at work, I spend a lot of time with people who are really, well, more of a working class kind of environment. My father, you know, never went to college. He's a working class guy. My mother went to college. She was very educated, and so I've always found myself just having a little bits of lots of different groups and being able to kind of sit, how do I fit into this group today? And then I'm going to this other group and I'm going to change a little bit. And how do I fit into this group today? Guess I've always done that. I've never found someone who's exactly like me. I just have bits and pieces of a lot of things. Yeah, well, it's.

John Shufeldt:
Actually worked well. So let's talk about Khadijah first because that leads into QC. Tell us how you founded Khadijah and what it did and then how you got out of it.

Ross Bundy:
Yeah. So Khadijah, it is a journey. And it's one of these things right now has a really great story. We were very successful, but it was a lot of failures until we succeeded. There's all this really amazing academic research around carbon nanomaterials. That's where my co-founder at the time, Brett, had built his PhD. And so we said, hey, we're going to go build a sensor on this. And there's some doctors that were really interested in a couple of the things they published on, and we're calling them up. And so we said, let's build on that. And we initially founded the company to focus on diagnostics. The sensor had a lot of opportunities in diagnostics where you can do some really unique things, but it is with a material called graphene. So one of the things I learned the hard way initially set out and said, we're not going to go out and build graphene. We're going to try to buy it from people. We're going to focus on building the sensor and really meeting the needs of our customers. And we started talking to people in the space and realized that this is one of the first things I realized coming into science, that there's a lot of hyperbole in science where people publish on things and they tell a story about the value of what they publish. But oftentimes that story doesn't really resonate with what the real world is, just something somebody made up. Graphene is a lot like that. Everyone says, oh, it can do all these amazing things. If only we could produce it and scale it. Well, I couldn't. Coming out of manufacturing from several different industries, when I was talking to the people working on graphene production, there wasn't a single one I could trust that understood what quality meant, which was really what my opinion was.

John Shufeldt:
So back up for a second. For those of us twos, what is graphene?

Ross Bundy:
So graphene is a material. It's a one atom thick sheet of carbon. What it allows you to do in. There's a lot of things that they say graphene is good at. It has all these incredible, amazing properties. None of those have really translated well into applications. But what it does do as a semiconductor material is because you're at the one atom thick level, you're able to leverage some things that start happening at almost like the quantum level and bringing it. Up to a little bit more like the macro level. And in our case, as a biosensor, it's carbon, which means we can integrate carbon chemistry like DNA and antibodies and proteins into a transistor. It's stable when exposed to a very complex environment like human blood or samples. It still conducts just fine, and it's extremely low power. While very sensitive as a conductor, essentially what that means is a biosensor from a biologist perspective is you don't really need to do a lot of things to modify the sample at all. Like most sensing technologies, you've got to modify things a lot, like you got to amplify DNA or proteins, got out all these labels and do all these things to try to make a visual signal that you can read. With an electronic system like this, you don't need to do anything to modify it. You can attach it to the protein. We use a lot of analytical techniques that are pioneered by the telecommunications industry, the analog semiconductor industry, that allows us to boost our sensitivity electronically and not have to boost it chemically, which opens up a lot of opportunities for building really sensitive complex assays in very complicated samples. And the instruments cost almost nothing. They're just circuit boards.

Ross Bundy:
They're super low power. They're very basic. And so it creates the ability to bring complex biochemical analysis. It lowers the accessibility of that. And, you know, almost an average user could just put something on a chip and it'll read it. And because the chip does everything, we can use some really interesting sort of analytical techniques to just give an answer that's relevant. It makes what is a very difficult to field, like biochemical testing or genetic testing, accessible to virtually anybody, and able to see some really unique things that we haven't been able to do before. One of the big things in life science is the sensing measurements that have existed in the past, because they have to do all these complex chemical ways to boost the signal. Those tend to interfere with other types of biochemistry. And as a result, we've divided life science into verticals genomics, proteomics, metabolomics, microbiology, the cell environments, all these different things. It's mostly because that's an artificial silos, which we make because of the sensing techniques that we do. The advantage of a technology like this is those silos mean nothing. It doesn't matter. You can put anything down on the chip and it reads how it all interacts in the type of matrix it would be found in life. And so you really get a very relevant sensing modality on how verticals that typically don't interact in the fields. Actually, we can see how those interact in real life, and we do it with inexpensive electronics and really complex analytics and mostly software instead of complex, expensive tools and things like that. It's really an accessibility and complexity and relevance kind of thing that graphene enables us to do.

John Shufeldt:
All right. So you talked to a bunch of graphene producers didn't trust any of them. Yeah.

Ross Bundy:
And so we became a manufacturer because we were forced to we did something really different than most people in the graphene space. They all said, hey, we're going to go build a foundry and said, hey, we're not going to build a foundry. We're going to go produce this by using other people, because the graphene is 1 or 2 steps. The wafer is a few hundred steps, but they're all skills that exist. Other people know how to do it. And I'm like, well, I could get really good and spend a lot of money figuring out how to get really good at wafer silicon oxide passivation. Or I could just buy it from somebody who's already good at that. Why would I get good at that? There's other people who can do that. And so we built more of a supply chain model where we took what we knew about graphene and found some mEMS style sensor foundries and said, hey, this is what we're working with, and let's use standard processes in silicon, but try to apply it to graphene. And we had to make some adaptations, and we invented a bunch of new things in order for it to work, but it allowed us to actually fit graphene into the existing silicon industry as opposed to setting up really proprietary stuff. And we did it really on the cheap and got it scaled for virtually nothing. But again, it was using a lot of supply chain style approaches is using things like the Theory of Constraints and Lean Six Sigma process. I joke that I combined what I learned in canned tuna and shipbuilding, where in shipbuilding you break down building a ship into a series of chunks, and then each chunk comes together, and then the bigger chunks come together, and then it comes up and it's a ship.

Ross Bundy:
But that allows you to control in an isolated environment, a certain step, and then you can drill down to any problems and fix them without having to reinvent the entire process. And so we built a model based on how we learned things in shipbuilding. But we had unknown inputs and unknown outputs because everything was new. So I modeled that on what I learned in how to manage the supply chain in canned tuna. I fitted all those learnings together and it worked and we put it all together. The whole supply chain, we were scaling, we were producing 10 to 20,000 chips a week, which was more than the entire world combined in every academic university everywhere. And that was just every week that we were doing that. So we built that, tried really hard to go into diagnostics. This was during the Theranos era, so that was very challenging to get into. Diagnostics. So we took a step back, built a life science tool, sold several of those. There's customers still using those tools, but found a lot of people were coming to us saying, hey, that sensor would be great in this market or that market or that market or that market, and there's all these different markets. And we said, okay, maybe we need to really own this. So we decided to really lean into being a chip company and saying, we'll partner with companies that know their markets and let them bring the technology to the market. But we're going to help build that platform for them and then support them as they go sell to that market. And so we transitioned the company into the name Cardea and merged a few companies together and built that partner model.

John Shufeldt:
So you're kind of a white label chip producer.

Ross Bundy:
Yeah, that's what Cardea was. Think of it like an Intel inside or like Snapdragon on the back of your phone, like Qualcomm. It's the same kind of thought. But we're Qualcomm is that for telecom and Intel is that for most things we were that for biology and biochemistry. It's still coming along. Biochemistry and the biology world has a lot of things to kind of work on. But we made a lot of progress. There's a lot of interest, a lot of different applications. And it was growing and it's working. And then there were niches that we saw that were opening up that no one was really pursuing or missing, because one of the things we were getting by opening this up to people to come use the platform is we were getting market knowledge. We started seeing where things were open. We said, oh, we could actually build some companies based on this. And so the Crispr idea was born out of that. We did some early tests in the market and saw some things that made sense. And we said, all right, we're going to build this as a company and get going on.

John Shufeldt:
My knowledge of Crispr really stems from Walter Isaacson's book about Jennifer Doudna called Code Breakers, which if you haven't read it, you should read it, because it's amazing. And I went to medical school a zillion years ago, and this is all new. After I read that book, that's when you and I got connected. So I have a working knowledge of Crispr. But why don't you first give an overview of kind of Crispr and what that means and talk about your process?

Ross Bundy:
It is really important, I think, that people understand what Crispr is. And fundamentally, one of the things I've learned being an entrepreneur is that we all talk about value and where is value. And I actually like to divide value into two groups. So there's intrinsic value and then there's derived value. So Crispr has no intrinsic value. It is a derived value. Because what is really important and what people have been trying to do for decades is saying, if we can actually change the DNA of cells, we can change how they function, and we can then create new things, new organisms, new opportunities that we've never, ever seen before. There's been a lot of attempts where people have been working on GMO crops and gene therapies. These have been coming around for a long time. There's been other forms of gene editing, but they're very artisanal, like spend a ton of work to make one thing that can only do one thing at one time, a little bit on the history. One of our advisors for Crispr actually discovered Crispr was a guy named Rudolph Barrangou. What he found was that bacteria have this ability to sift through viruses and remove the viral DNA from the bacteria and repair it back to the bacteria's normal DNA. And he's like, why are these bacteria doing this? And he found these Crispr molecules. And then he's worked with Doudna. He worked with several others. But they said, hey, this sifts through DNA and it finds a sequence and it removes it and the cell repairs it. And what Jennifer Doudna did was say, well, okay. But with the advent of synthetic biology, you know, the way Crispr works is there's what's called a CAS protein.

Ross Bundy:
There's a bunch of these now, and it's kind of like the engine. Right. And then what the engine goes and finds is this piece of guide RNA. So the way the bacteria works is a virus comes in and it doesn't like that virus. It holds on to a piece of the virus's RNA. So then it searches through the genome. And if that RNA matches to something in the bacteria's genome, it removes it. What Jennifer Doudna and Emmanuelle Charpentier realized was that said, hey, we can make that RNA synthetic biology, we can make RNA any day now, and we can put that in the CAS molecule. And now we can use Crispr and programmatically target parts of the human genome and edit out people's DNA. And that's her paper was literally a programmable gene editing tool is the title of it. So you could actually take this like a platform and target any part of the genome. And that's what won them the Nobel Prize. So obviously they're not talking about that. And that's where it's come up. And there's so many therapies. Now obviously genetic disease is one of the big ones. But also can we remove parts of cancer tumors that make them more susceptible to chemo? Can we remove viruses from people's DNA and cure people of HIV? And there's so many opportunities in AG. But it goes back to this core thing. If we can control the genome of cells, we can force these organisms around us or cure things from our bodies that we don't want. And Crispr might be able to do that if we have full control of it. That's what's got everyone so excited about the field.

John Shufeldt:
And that is pretty exciting. The interesting thing is you mentioned HIV. That was that Chinese scientist who got in trouble. Shanku, I think is how you pronounce his name, who spent, I think, three years in prison in China, in he's now out and.

Ross Bundy:
Now he has his own company working on. Gene editing therapies. So it is the downside to a powerful tool is that it also opens up some potential unethical things. I think that guy is not the problem. The problem is how many people did we not catch that are like that guy and are doing things that we don't know about? That is the thing that can be frightening. Anybody can work with Crispr.

John Shufeldt:
Yeah, well, he published it, and that's why at first he was celebrated, as I recall, and then he got thrown in prison in 2019.

Ross Bundy:
Yeah, yeah, it created such an ethical discussion. But I think the bigger concern again, is, you know, no one knew what he was doing until he did it. And then it was over. And so that just says, what are people doing that we don't know about? And given the uncontrolled nature of Crispr, then there is this need for ethics and control. And that's a big part of where the government plays a role. But even the government doesn't quite have the type of oversight to watch everybody else that's out there in some ways. And this is starting to lead into Crispr in some ways. There is a place also for third party agencies to help observe what's going on, because sometimes private agencies have the ability to see things at a much more fine level than the government, which tends to be more of a broadsword approach. Companies have ability to be a bit of a scalpel, or at least raise a red flag and let the government do its job. So there is an opportunity, and definitely a need for someone to keep an eye on what's going on without a wedded kind of purpose to just their own gene editing career. Right.

John Shufeldt:
Why do you think people I mean, here's all the time, no GMO, non-GMO, why do you think there are some groups that are so freaked out about GMO food?

Ross Bundy:
Boy, that's a big topic. But you could say it's a very related to people who are absolutely afraid of nuclear power, which by the numbers, is the safest form of power in human history. It's just associated with certain things. But it also speaks to one of the needs for precise control, reliability and third party validation. Because when you're talking about editing your DNA and it goes wrong, can you fix it right now? I don't think so. When people today know enough but not know that this is something that could be really dangerous, but they don't know nearly enough to know that maybe it shouldn't be. And there's been too many instances where people who have really good intentions and are highly technical, but are still human and make mistakes, and they're catastrophic effects. The biggest issue, not just related to GMO in particular, I think people get worried because they're like, we don't know what it means when you cross a sea slug with corn. And what does that do, right? Probably nothing. Our bodies break all that stuff down with all these complex acids in our stomach, but nobody really knows. And there are people who take that. Nobody knows as we shouldn't do anything because there is a risk. The big one, I think also in the therapeutic side was this gene therapy trial about 20 years ago, where they were showing such tremendous progress in animal models, and they went straight to humans and kids died and got cancer, and it shut down gene therapy for decades. It just shows. Here's some amazing people.

John Shufeldt:
There's a sickle cell, wasn't it?

Ross Bundy:
No, it's a disease. I can't remember the name of it, but it's a genetic disease where people are unable to process ammonia, build buildup in their bodies, and usually the children who have that die. But some children have it weak enough where they live, and then they have really, really strict diets and all these other issues. So they said, hey, maybe we can help these kids that have actually survived into at least teenage years or their 20s remove this completely from their bodies. One thing that happened was the kid who died. They used a virus as a delivery mechanism, and it appears it just planted the DNA all over parts of his DNA and kind of random numbers. It was totally uncontrolled, and his body just started breaking down because he had so many different things happening to his genome that things just started this cascade effect. And he was gone in about 3 or 4 days after that. It just goes to show that no matter how amazing our science is, even the best scientists can be human and make mistakes. And the people who are on the receiving end of this, they're like, well, how do I know you're still a human being? How do you know you've done everything and there's real risks, there's real issues there. And so that's where making sure that as many potential knowledgeable risk factors are taken into account in order to make these safer and acceptable is necessary.

Ross Bundy:
I recently met a couple whose children have sickle cell, and they knew about the Crispr therapeutics therapy, and they said, under no circumstances I'm going to do that. They went through a much more invasive bone marrow transplant, because at least that has worked for some people, and they did that for their four year old daughter, and now they're considering it for their next youngest child, who also has sickle cell. And they're like, there's no way I'll take that Crispr therapy because I don't know what it does. And they're both scientists. And I was just like, wow, that's interesting. But it just tells you that much of what happens in the scientific field gets wrapped up in the power of what we can do. And sometimes they might as humans, we might skip over and say, well, yeah, but do we really know about this? Should we or do I have a stock price to keep up? I need to keep doing. Trials forward, or keep showing this promise or all these other financial demands, and that can sort of allow them to slip or make some mistakes. And there's real consequences that someone has to live with.

John Shufeldt:
As I recall, they've done a lot of gene editing on sickle cell folks. I think there's a pretty large number now of people that have been cured of sickle cell. Does this only work for single gene edits, or can it work for combinations as well? Because the single genetic diseases seem like logically, that's relatively, I don't want to say easy, but straightforward to fix.

Ross Bundy:
Relatively easy. I would say relative is the key word for sure. There are people doing multiplex editing. It's a lot more common in agriculture because obviously the ethical concerns are lower. Multiplex editing does not work very well. Whether you're trying to mix six different SNPs together and target six parts of the genome or something like that, generally you only get 1 or 2, and that's actually an area where we're able to start figuring out why that's happening and some of the things that we're doing, the other issues, obviously, to your point about sickle cell, yeah, Crispr Therapeutics and Vertex, which that's the therapy. They've cured 70 people. Yeah. Sickle cell completely blood transfusion free. However, there's another company called Graphite Bio. They do this cell therapy. They're editing bone marrow cells. They edit them outside of the body. They put the bone marrow cells back in. And this first patient they dosed, they voluntarily stopped the trial because that patient was producing no blood cells. Now you have a really, really big problem. So it isn't quite as simple, even though that Crispr Therapeutics has done incredibly for the field and for themselves, it isn't just a slam dunk. Even with something like sickle cell. And there's a reason they targeted sickle cell, it's a lot easier to target than most of the other things people want to do. It is a risky endeavor, even with the single edit things. And then, yeah, there's a lot of different strategies out there too.

Ross Bundy:
It's not just targeting, say, blood cells. I really, really like a company. The name slips my mind. Right now they're targeting HIV, but they have to remove HIV from every cell in the body. Boy, that's a big swing and kudos for them for going for it. But that's an enormous challenge. I really like the companies doing cancer because they don't need to be as successful. They're really targeting the tumors. Most of the strategies are targeting the tumors to remove the tumors resistance to chemotherapy. So it's all about can I make chemo better? And if I have 40% success rate just on the tumor, that means the chemo is 40% more successful. It's actually a good strategy. It's a low bar right. And a lot of the patients they're usually targeting are usually in stage four. Anyways, you're talking about maybe six months to a year of life. So if there's an off target effect and the person sadly to say doesn't have that much longer to go, so it's probably not as big as, say, editing a five year old child who has a 5060 year life ahead of them. There's a lot of different ways that people are going about this. Some are safer than others, some are riskier than others. I do think a few people are really swinging for the fences to keep the promise of the field alive, and there may be some real risks of what they're doing, but there's also enormous potential as well.

John Shufeldt:
Well, let's talk about Crispr, because when I first heard the pitch, I'm like, yep, that's it. This is what's needed. And I have an incredibly rudimentary knowledge. So explain what Crispr does and then what its impact is.

Ross Bundy:
Yeah. So there's kind of two ways they like to talk about it. And I'll, I'll I'll talk about it. One thing is in my opinion is really more the boring way. So yeah, we're using the sensor technology that came out of Cardea to do what we do, and it creates this unique type of measurement technique that allows us to measure all the editing activity. But on a chip, any target DNA, any chemistry. And we can start Quantitating. What are the sort of gears, what are the variables that, you know, that actually drive good and bad outcomes in different situations? And with enough knowledge of that, you can start building algorithms that take inputs and you measure something about a person, you put them in and it says, okay, you need this kind of chemistry to deal with these situations. And here's how you monitor it. So, you know, that's the the bottoms up approach, which I think is less exciting. I think the more exciting way to talk about it, though, is what we're really seeing in Crispr is enormous potential. And it's exploded onto the field. And now we're moving out of the excitement phase and starting to move to a maturing phase and an industrial phase. And what is that difference? So I go back to the things that I've done, like shipbuilding and consumer packaged goods. Things have been around for hundreds of years, and these processes have been around for hundreds of years. What has gotten those industries to be so successful in everything from semiconductor to retail to clothing, is about understanding how you take a process and you understand how every step you do correlates to what the end outcome is going to be. And you don't do that in life science very often. You absolutely do that in gene editing. They mix everything together and then just measure the result.

Ross Bundy:
But you never really know if it was good or bad. Where do you stop? Where do you investigate in order to turn a good one into a bad one, into a good one? Or if I know it's good, how do I get that good and reproduce it? How do I control? Roll. What I just did. What did I do right? I don't know. And what our measurement allows the field to do is to really start understanding things as simple as, where did I order my raisins from? How did I store them? How did I prep them? Versus if I want to do something complex? Like how do I mix multiple different reagents together to get to a multiplex edit that's actually going to work, and the whole range in between? We can start helping the process to understand how do you actually control that process to get to an output that you want, instead of just sort of mixing together and hoping for the best, you take a step and you knowingly are moving in the direction you want to go because you measure it and you know the results of what you did. And what does that mean for the next step, for the next step. So when you get to the end outcome with a cell, you get to where exactly we're expected to be. That's kind of the opportunity that the measurement techniques and the data allow us to do that we're now bringing to the field. But it does mean we have to educate the field about a lot of things that they're doing that they don't really know that they're doing, and we need to help them kind of understand, hey, there's a lot of other areas you need to actually control.

John Shufeldt:
Okay. Let me ask you a very basic question. What level of accuracy does Crispr QC correlate to? In other words, where was it prior to this? Where was it after Crispr QC?

Ross Bundy:
I think the first step to say is what is accuracy in gene editing. So the unfortunate thing is that good means an 80% success rate usually, and 80% of what what most people do is what's called an Indel score or a knockout score. There's similar, but they mean slightly different things. But really they mix the chemistry together. They put it in the cells, they wait for some time, they culture up the cells, and then they extract some DNA and sequence the DNA, and then they plug it into a tool. And that tool gives them a percentage score. And the percentage score is what percent of cells after multiple generations result in the desired outcome.

John Shufeldt:
Right. The sequence. Yeah.

Ross Bundy:
Yeah. Right. And the problem is that no one really knows what those scores mean. They're all derived scores. And there's a lot of subjectivity in that process to get to the result. So did I get a good result because I cultured eight times versus five times, or do I sequence this way, or did I use these reagents this way or what was going on? Generally, people use those terms in very semi-quantitative ways, right? I've asked these question to some of the best gene editors out there, and we ask them, what does it mean to have an 80 versus an 85%? And they're like, oh, that's no different. Anything above 80 is good, anything below 30 is bad. Anything in between will go to if anything above 80 fails. And really that's in the context of just guidances. And they rarely talk about CAS proteins. They really talk about anything else. So that's the bar I got to hit is basically quartiles and all these different things. So what we've done with it and what we're finding is that not only can we very nicely correlate to different cell types in those same quartiles, but rather there's a couple different ways of looking at every sensor that we run, which is about magnitude and efficiencies and rates of editing and these different things. And you can actually put together when you look at that, not only can you easily match to those quartiles, but you can actually start putting a story together. For example, one of the work that we've done we found is the different guide RNAs we worked with. They have their cell results and one is all over the place. And we looked at it and we found that it edits extraordinarily fast and it's very loose at binding to its target.

Ross Bundy:
So what does that mean. Well it now says, hey, if it loosely binds to its target, it means that it could bind to other parts of the genome loosely. And if that's enough, a fast editor says, oh, let's just break it. Oh, here's another spot. Oh, let's break it. Oh, here's another spot here. It's break it. Or the other thing that I've heard people get concerned about is like a fast editor. It lingers around after it's been repaired. The rnps are still there. So then you say it loosely bound. And now I've got to repair to a sequence that's like the one it found. Oh, it just latches back onto the repair and it breaks it, and the cell comes in and repairs, and then it breaks it again. And the cell repairs. Then it breaks it again. Before you know it, you've repaired six, seven times in the same spot. And now the repair mechanisms cause a problem because it's had to break and repair so many times. So you've got like one of these that's a very loose binder, very fast editor. It's just very difficult to control. And all the best ones are a reasonable amount and a reasonable level of binding. So you can actually start putting a story together to start saying, why is this going wrong? And here's different areas that we can now understand about what our chemistry is doing that's going to empower other parts of our process as we go. In a way, I would say we're matching easily to the low bar that the field has already set for itself. But I think we're showing that there's way, way more information that allows them to really understand what's going on and trigger certain parts to really drive good outcomes.

John Shufeldt:
What's been the hardest part? We were laughing before we started about the show Silicon Valley and how funny it is, but also how true it is. What's been your Silicon Valley moment with Crispr QC?

Ross Bundy:
The good news is I'm not as. Is new to this anymore since I have one company, so I've been able to avoid a few this time as a non-scientist working in science. I think the thing that's one of the more frustrating things for me is realizing just how much groupthink and how much wedded to their professional opinion. Even if you bring something new that a lot of scientists are actually not willing to back off of and gene editing, well, it's a large field. It is a niche field. There's a lot of new people coming in, but there's still a lot of experts, and the experts are controlling the language. But they've built their language on things that they did five, ten years ago. Okay, there's new things and there's new ways, and there's all sorts of new ideas coming into the field. And in some ways, we're challenging their careers and the things they've built their business on because we're telling them that some of the things they did five years ago are not necessarily accurate. And as a result, it does create some challenges for us to get to some of those folks. I tend to have more results with people who are reasonably sophisticated, but still new to the field and open to new ways, new ideas of different things. But some of the leaders in the field in some ways feel challenged by what we have to offer. I think the craziest thing for me is looking at the leaders in the space who are essentially startups. I mean, Crispr Therapeutics and Intellia and Editus are all multi-billion dollar companies that are public, but they're wedded to this, so they still act in some ways, like startups. They don't want to know what we have. The FDA hasn't caught up to putting out regulatory guidance and safety guidance, so we slow their trials down. If they have to take a moment and take a look at their controls. And that's not going to help them in a lot of ways, but you improve the accuracy.

John Shufeldt:
So are you really slowing them down? If they're running at a 45% before and now they have a 95% or an 85%, arguably you'll add value. And one of the things we talked about is you capturing a piece of the value you add.

Ross Bundy:
Yeah, I think when we can prove it to a greater degree and the FDA starts putting their foot down on things, the FDA is taking a measured approach to this. But when the FDA starts putting their foot down, then they're going to have to come around and come work with us. But until then, because the FDA is still at a draft guidance level, still trying to get their arms around the field, then what matters most to them is actually speed to clinical trials, not necessarily accuracy, because that's what keeps their stock price up and that's what carries the money. It's unfortunate for me to say that, but that correlates to the behavior I've seen from them as well. What's going to happen. And the big companies are in some ways that way too. So that means a lot of the smaller companies who need to catch up are more receptive to the things that we have to offer, because they realize they're going to cut through a lot of the big rocks that those other companies stumbled into. They can just bypass them just by working with us. So we're going to have a lot more success with a lot more of the new entrants. And the legacy entrants are going to be a little more challenged.

John Shufeldt:
I was laughing when you said you were surprised at how entrenched some of the scientists were about something new, and I laughed because physicians generally, and probably scientists, many of us aren't early adopters by nature. There's a lot of experience I've had when I pitched them something thinking, oh my God, this is such a slam dunk. This is so obvious. It's staring you in the face. And I'm like, yeah, no. Yeah. What? Yeah. And so yeah, I think you're right. Maybe they're entrenched for good reason because a lot of things Theranos that you mentioned, I mean, remember when she came to Phoenix and sold at Walgreens and pitched to our legislator, all the physicians? We all rolled our eyes because at the time everybody said, yeah, that's not possible. Yeah. And in the back of my mind, I thought, God, maybe it is. Maybe I'm missing something. But then people would show up in the emergency room with these labs that were incompatible with life, and they'd say, I went to Walgreens and got my Theranos test, and this looks bad. Yeah, that looks bad. Like you wouldn't be alive if that was the result. So then you repeat them and they'd be fine. And then it started to unravel for her. So maybe it's good that some people are a little set in their ways, but it's, I guess, finding that balance. I always say strong convictions, loosely held like convictions, are great, but you have to be reasonable. If someone presents objective data that you can at least look at them and say, yeah, maybe time to change.

Ross Bundy:
You know, I had to deal with a lot of challenges with what Elizabeth Holmes did, but to give her some credit, she was resilient in challenging what is essentially an entrenched lab testing industry. That doesn't change very quickly. And she did make a dent. Now, if she only had great technology, it would have been amazing. But what she did do to her credit is break through some of that and actually get people to start taking her seriously again and again and again. And it took so much time for her to do that, and it's not easy to do so. I will give her credit for what she did to sort of challenge the established model.

John Shufeldt:
I have to say. And I've read all the books about her and saw the documentaries. You're the first person I've ever heard to give her credit, which that's a good way to look at it. I can't get there intellectually myself. But you're right. She definitely made a dent. I mean, it was a dent nobody needed. But she did, through resilience, make a dent.

Ross Bundy:
Yeah. Look at people in multiple dimensions and things she did wrong. But there's always things to learn from certain people too. And she did at least make. People consider it. The legacy of her situation means that people are taking a solid look at testing and saying maybe her technology was bad, but the message wasn't wrong. Maybe we could do something. Maybe we could expose this to, you know, closer to people and make these express clinics more available and these kinds of things. A momentum did happen because of that, which she was a big part of getting that part started. I'm not a fan of Elon Musk, but I do drive an electric vehicle, and that's happened because of what he's done. Even though I would never build a company the way he does things. You can't deny the results of the change that he's brought into the world because of that storytelling and challenging the established quote. I try to learn from people and what they did do correctly or what they did do. That is admirable, even though everyone's complicated and nobody's 100% admirable. You know, it's.

John Shufeldt:
Funny you just said that. As I mentioned, I've finished Walter Isaacson's book on Elon Musk and had a Tesla since 2013. And I've always thought, okay, Elon Musk is a lunatic, brilliant, but a lunatic. After I read the book. I'm an Elon Musk fan now. Oh really?

Ross Bundy:
And maybe I'll have to get the book.

John Shufeldt:
Then, because you kind of are building a company like Elon Musk now, you're not probably as mercurial as he is. I'm sure you're not, actually. But you are doing something that challenges the status quo and is going to ruffle some feathers, which he does, and pretty much every company he builds. I mean, think of PayPal, the banking, electric vehicles, space X. I don't know what to say yet about Twitter, but he's certainly challenging the status quo and has learned from it. So, you know, I wouldn't sell yourself short. You're Musk esque.

Ross Bundy:
Okay, well, like I said, there's a lot of things to admire about him. I could not build Tesla the way that he did and he's done a great job. It's amazing. So that is a credit to him, even though I probably would not get along with him on a personal level, I can't admire what he has accomplished. It is incredible. Yeah, and that's.

John Shufeldt:
What I took away. I've built companies before. I can never do it like he did. That's just not my personality. Yeah, but you have to say, at least for him, it works. Now, there's a lot of chaos in his wake, and I hope that's not me. But he does make a dent in the universe, as Steve Jobs would say. So what's next for Crispr? Honestly, the.

Ross Bundy:
Biggest thing I'm looking forward to is hiring. I find that the thing I most enjoy about being an entrepreneur, and one thing I do pride myself a bit on, where I wouldn't call myself a two is I feel like I've really learned how to assess people really well, understand their strengths, understand their weaknesses, and build a position where people's strengths are really magnified and minimize their weaknesses and shore them up with someone else where they're strong there, and really build a multifaceted team where people are motivated to really do those things. You know, a guy I trained who had no real work experience was our VP of production in the early days, and he ended up getting recruited to run Intel's ten nanometer line with 200 people reporting to him. He's now at another semiconductor company running all their operations. A young woman that I trained who worked for me, is now the director of operations at a at a major hospital chain in the Northern California area. A woman who worked for me in marketing is now sought after, recruited head of marketing of a company that just exited and consumer life science people that I've worked with. I love how they've really found their passion and their capabilities, and when they do move on, they move on to really amazing things. And the people that I admire and I'm like, boy, but I hired you.

Ross Bundy:
I was able to put you in a great position to really show off your strengths. And yeah, you got recruited away from me. But look at you. You're amazing. And so I do love bringing in new people and building that team. And I've got the team planned now. So as we finish out the financing over the next couple of weeks, I've already started one job position. I'm recruiting for others, and then I'm really looking forward to putting the team together and seeing how everybody sort of bites into their role and starts running with it, seeing people find their own value. Because a lot of times companies, particularly larger companies, are pretty bad at that, at positioning people where they really find that value. And in small companies, you can kind of craft a role where someone's value is really realized. Then seeing people start realizing that and being like, wow, I really do great things. I'm amazing is one of the most fulfilling things that we do. Not just building companies, but really building people is one of my most exciting things that I love doing. As we go into this growth phase, I'm like, oh man, we're going right to the part that I love the most. This is the best part.

John Shufeldt:
So that's awesome. So just kind of wrapping up because people are going to want to learn from you. What advice do you have for folks who are considering doing their own startup?

Ross Bundy:
The first thing I tell people is don't do it. It's not like being Elon Musk or Jeff Bezos. Even those guys had some really, really tough nights. It is very much an identity. It's not a job. Don't say I'm an entrepreneur. That's my job. It is my life. You bring it home with you.

John Shufeldt:
It's 24 over seven.

Ross Bundy:
Yeah. And I use this term recently with somebody that it's really critical that you build a tribe of people. My family is very important to me. I have certain friends that don't work where I'm at, but I go and when we go vent about stuff, I'm venting about these things. I find other CEOs that get it, and I can just vent and they can vent to me, and we can kind of talk about those things, like understanding how to balance all the stresses and all the challenges, and kind of lean on forming that tribe of. People. That is, your support network is really, really critical to being able to come in every day, mean, stable and not feeling swinging and all the stresses and challenges. But I'd also say there's a lot of people who are really, really good at what they do, but they're not necessarily good at understanding how to translate that into real value. And you don't need to be an expert at those types of things. I often tell people, my dad is one of my biggest advisors because he never went to college. And so I call him up and I'll be like, let me practice what I'm about to pitch to you. And if he's like, don't get it, then I'm like, okay, I made it too hard.

Ross Bundy:
Let's change the story until anyone can get what I'm trying to say. When I've learned some new science, how do I explain this so that average people will care that aren't experts in the field? Then now you're being able to tell that story and lead and do these kinds of things. What you find is also there's a lot of amazing science that is orphaned. It has nowhere to go. There's an expert there that has nowhere to go. And so there's a lot of good scientists who want to take their science somewhere, but they have no idea where to get started. So anyone can do it. Anyone can go be the business side of the face of it, but it requires having that responsibility. You know, understanding the mental challenges, understanding how you have to support others. Your job is to support everybody. Your job is to be responsible for what everybody's doing, but you can't actually do any of it. In some ways, it can be one of the most rewarding things that anybody does, but you don't have to be an expert in the field. Like, didn't know anything about Crispr and gene editing until I got into it. But I know a lot now because I've worked with and listened to a lot of very smart people, and that's cool.

John Shufeldt:
So this has been amazing. Thank you for this. Where can people find out more about you and Crispr QC? And we'll put this in the notes as well.

Ross Bundy:
Yeah. Check out our website. We're moving our website and our brand into a little more of an educational role about gene editing, not just what are the nuances that things that our customers should be aware of, but also how does everybody understand what this is? Because it is going to touch everybody when it comes out. So we're moving a lot of our message to that direction. So keep an eye on us there. I'm pretty active on LinkedIn. That's where you can find most things about me and where that's going. And I do respond to actually people when they reach out to me on LinkedIn as well.

John Shufeldt:
So very good. Well, Ross, thank you. Good luck. We're both counting on this. I know, but good luck. All right.

Ross Bundy:
Thanks, John. I'm looking forward to working with you for the next couple of years. It'll be great.

John Shufeldt:
We'll have a lot of fun. Thanks. Yep.

Ross Bundy:
Thanks. Bye.

John Shufeldt:
Thanks for listening to another great edition of entrepreneur to find out how to start a business and help secure your future. Go to John Shufelt Webmd.com. Thanks for listening.

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