Intro:
From the library of the New York Stock Exchange at the corner of Wall and Broad Streets in New York city, you're Inside the ICE House, our podcast from Intercontinental Exchange on markets, leadership and vision and global business, the dream drivers that have made the NYC an indispensable institution of global growth for over 225 years.
Intro:
Each week, we feature stories of those who hatch plans, create jobs and harness the engine of capitalism right here, right now at the NYC and at ISIS 12 Exchanges and six clearing houses around the world. And now welcome Inside the ICE House. Here's your host, Josh King of Intercontinental Exchange.
Josh King:
The backdrop for today's episode begins back in 1990 with the largest scientific collaboration in the history of the world, the goal to map the entire human genome down to the last of the more than 3.3 billion base pairs of DNA. Here is President Bill Clinton in the White House with Dr. Craig Venter, President of Celera Genomics and Dr. Francis Collins, Director of the National Human Genome Research Institute back in June 26th, 2000, announcing the completion of the first survey of the entire human genome.
President Bill Clinton:
How far we have come since that day. In the intervening years, we have pooled the combined wisdom of biology, chemistry, physics, engineering, mathematics, and computer science, tap the great strengths and insights of the public and private sectors. More than a thousand researchers across six nations have revealed nearly all three billion letters of our miraculous genetic code.
President Bill Clinton:
I congratulate all of you on the stunning and humbling achievement. Today's announcement represents more than just an epic making triumph of science and reason. After all, when Galileo discovered he could use the tools of mathematics and mechanics to understand the motion of celestial bodies, he felt in the words of one imminent researcher that he had learned the language in which God created the universe. Today, we are learning the language in which God created life.
Josh King:
The language in which God created life. No doubt there would soon sprout a robust garden of business opportunities flowering from that language. Genomics, the study of the structure, function, evolution and mapping of the genome has exploded into a multi-billion dollar industry taking on the medical diseases and maladies that affect millions of patients across the world every single year.
Josh King:
Freenome, one of the best known companies in this space has set out to use genomics to identify cancer before medical professionals ever thought was possible. Their platform and tests can also show what treatments would be most effective and allow care to commence even when the disease is in a more curable state.
Josh King:
The result is a cancer diagnosis and treatment that is minimally disruptive to the life and long-term outlook of the patient. The what, when, where and why of the company is pretty simple, but the how may be the most complex topic that we've covered here inside the ICE House. Our guest today, Gabe Otte, co-founded Freenome five years ago.
Josh King:
And as CEO, he helped us secure its growth, both in the lab and with top venture capitalists in Silicon Valley and beyond. He joins us today to break down the science behind stopping cancer and how Freenome is creating a platform solution that is using machine learning to become more efficient over time. Our conversation with Gabe Otte right after this.
Audio:
It's more than an iconic building or a global financial marketplace. It's anywhere technology, commerce and people intersect. The innovation that makes people's lives better, dreams that were once impossible are now realities. At the New York Stock Exchange we help tech companies flourish and change the world. So go ahead, bring those ideas to life. We'll bring it to market. We are living tech.
Josh King:
Our guest today, Gabe Otte, is the co-founder and CEO of Freenome, a biotech company that leverages machine learning to study bloodborne DNA to detect cancer. Along with co-founder Riley Ennis, Gabe started Freenome in 2014 and has raised nearly $240 million from Andreessen Horowitz, Verily, Google Ventures and others. Welcome Gabe Inside the ICE House and to the New York Stock Exchange.
Gabe Otte:
Thanks so much for having me.
Josh King:
You were probably about 10 or 11 years old on that day in 2000 when Craig Venter burst onto the scene, having helped map the human genome. Did any of the buzz register with you at the time, the earliest introductions to biology that we all had in high school or before then?
Gabe Otte:
I actually remember them talking about the human genome project, as you said, when I was very young and it actually is largely responsible for me getting into science. And in fact it was really amazing because a couple of years ago I had the pleasure of interviewing Craig Venter in a fireside chat where I got to do the interview. And I thought that was a nice sort of full circle because he was one of those people that inspired me to become a scientist.
Josh King:
I mean, when I read about an endeavor like the human genome project, the reported potential of genome sounds like impossible breakthroughs that remain in the distant future. But what are some of the use cases that you've already realized in those 19 years since Venter was in the White House with President Clinton?
Gabe Otte:
One thing that we found when we completed the human genome project is that our genomes are way more complicated than we thought. I remember people talking before the human genome project was complete, that once it was completed, that we would somehow know the sort of causes of all the diseases and we would be able to understand which genes affect these diseases and how to treat those diseases better as a result of that.
Gabe Otte:
I think when the human genome project was completed, it turned out to be way more complicated than we thought. There were only about 20 genes that are into human genome out of the three billion bases. And those 20,000 gene could only explain a fraction of the diseases when just looked at on their own. So I think over the last 20 years or so, it's been really this next phase of studying the genome of how does our DNA actually work so that we become who we are.
Gabe Otte:
And I think one of the realizations that we've had is how our DNA is used in some sense can affect who we are way more than what is actually in our DNA. And the how of our DNA is a little bit more complicated to study than what's in the DNA. And there's been a lot of interesting research in those fields and a lot of applications that have come from that.
Gabe Otte:
One of which is obviously a better understanding of how tumors form, how to detect them early, how to treat them, recognizing that tumors have a different DNA than the DNA that's in the rest of our bodies. Understanding the nuances of these differences and what they mean.
Josh King:
When a layperson thinks about DNA, the assumption is that everybody's genes are set at birth, but genomics have found that to be patently false. Why is that?
Gabe Otte:
I think it's interesting when you study genomics because every cell in your body theoretically, should have the same DNA in each one of our cells. But for example, your cells in your skin is very different than your neurons, right? Some of which can go from anywhere from like three to six feet down to very, very small cells, but they all have the same DNA. How does that happen?
Gabe Otte:
And it comes back to what I was telling you before of how our DNA is used is a very important part of who we become. And what I mean by how is the vast majority of the 3.3 billion bases that you talked about aren't active in every cell. So different parts of our DNA is active in different types of cells, which is what allows us to use that one DNA and be able to have all these different phenotypes.
Gabe Otte:
And so in sort of a similar way, it's really interesting for us to see how little changes in our genomes can cause a cell to start growing out of control, which then becomes a tumor, right? But those are really, really small changes that lead to much bigger changes on how that particular cancer cell uses its DNA in terms of which genes are active or not active. That's how it starts changing more radically, just from a few very small changes in the three billion bases.
Josh King:
Going back to what you were telling me about where you first started paying attention to what was going on in the human genome project, but more importantly to the world around you, the human body transmits 500 terabytes of information every second.
Josh King:
So the underlying problem with genomics must in many ways be a big data issue, which is where your expertise comes in. You released your first software program when you were about a we lad of 12 years old. How did you get introduced into programming so early in your life?
Gabe Otte:
I credit that to my dad. He was a philosopher at the University of California in Santa Cruz. Felt that it was really important for his kids, my brother and me to be able to think logically. And so he started teaching us a lot of these logic puzzles and logical proofs. And for a 10 year old, 11 year old, that was really abstract, right?
Gabe Otte:
To do logical proofs and theorems. I think as much as we appreciated those little puzzles, for me I needed something more concrete and he got me into computer science because computer science to a certain extent is an application of logic.
Gabe Otte:
And I loved this idea of you can type on a computer and when you're done, there's a product that you can look at and say, I made that. And that was a really exciting, exhilarating feeling as a young kid to be able to create something.
Josh King:
I read in an interview that you hid some of your coding from your high school classmates, but it was noticed by a well known company of developers. How did you end up snagging an internship at Apple while you were still in high school?
Gabe Otte:
So it goes back to the software that I released when I was 13. It was called OSX Planet. And it's actually what it did was quite simple. It put an image of the earth on your desktop with the current clouds and active volcanoes and earthquakes and things like that. So you got sort of a snapshot of what's going on around the earth.
Gabe Otte:
And your desktop would change throughout the day to reflect that. And a lot of people at Apple were using that piece of software at the time. And the internship, I actually got a call from an Apple subsidiary called File Maker. And those guys apparently were using OSX Planet on their desktops. And they found out that I was in Santa Cruz short ways away from where they were. And they just said, do you want an internship for the summer?
Josh King:
So you're an intern at Apple in the summer while you're in high school. How do you adjust to life at college after an experience like that?
Gabe Otte:
Well, I learned a lot in my internship. I think first and foremost the thing that was really helpful for me was that there was life after college. And I knew that sort of going into college, which was really an amazing leg up. I kept on working on various things throughout college that is creating something sort of concretely.
Gabe Otte:
And that was nice to sort of keep a hand in making things while you're learning a lot of theory and learning a lot of things from your classes. I think having that job early on made sure that I knew that all this theory that I'm learning in my classes is actually leading to something. And that was really motivating
Josh King:
After college you're in grad school, you're studying genomics and computational biology, which were both at the time relatively new disciplines. What drew you to study these topics from what appeared to be a bright start in the tech development field?
Gabe Otte:
I was always interested in curing diseases. I think a lot of people want to go into the biomedical sciences or become doctors. And I was no different in that regard. I wanted to figure out why these diseases happen to us.
Josh King:
Why?
Gabe Otte:
I guess I wasn't satisfied with just making technology. I wanted to do something that I believe was more meaningful. Not that technology isn't meaningful. It just, I wanted to understand what I believe to be more complicated than computers. I think computers, software engineering is really interesting.
Gabe Otte:
But understanding the human body, there's just so little that we know about it actually. So it was the big unknown that I thought computer science was going to play an important role in deconvoluting. And so that seemed to be the most interesting next step.
Josh King:
Before starting Freenome, you started a company called Acorn, which was a location based messaging app with your brother. This meant that even though you and your co-founder of Freenome, Riley Ennis were just in your mid 20s when you started the company, both of you came in previous experience actually running a business. What did your time with Acorn teach you about leading a company and working with investors?
Gabe Otte:
Well, I didn't know anything about business when Acorn started. And in fact, it was just down the street at 44 Wall Street is where Acorn was based out of. And we went through an accelerator called Dreamit, which taught me a lot of, I think the basics that you need to... I didn't know what a term sheet was, right?
Gabe Otte:
And didn't know anything about how to run a business. And they were really good about teaching me that and actually patiently so. Because you have a kid coming in that was really just interested in building technology, building interesting things, not really focused too much about how to make that into a business.
Gabe Otte:
And that's some of the earliest training that I had in terms of how do you build a team? How do you build a technology? How do you tell that story? How do you make other people interested in that story? I think those are all important lessons to learn when you're running a business,
Josh King:
What became of Acorn?
Gabe Otte:
So we exited the company about a year after we started the company. The founders went through separate ways. I think this, going back to the earlier point, I loved building Acorn for what it was, which was an interesting bit of technology, but I always wanted to do something more than that. And it took me a little bit longer to not listen to the naysayers.
Gabe Otte:
You tell somebody that you're going to cure cancer and they have one or two responses, which is you're crazy. Or they think it's a joke and they laugh, especially when you're young. And so I think it was more of a problem of conviction on my part of I am really going to do this and I don't know everything about how to do that yet, but I feel that that is really what I want to do with my life. So I'm going to do it anyway.
Josh King:
Bring us to that point where you are with Riley and the origin story of Freenome and who its formation came together in 2014. What was the moment in which you said, despite all the naysayers, despite all the obstacles that are out there, here, Riley and me, and we're just going to start thing?
Gabe Otte:
So Riley is the much more impressive of the two of us because that guy had conviction coming out of the womb. He started his first company when he was 16. I think he had like a first author of publication, peer reviewed publication when he was like 17. And that company that he started when he was 16, was in the cancer vaccine space, right?
Gabe Otte:
So he was already building these things way before I had come to that conclusion. And he was actually part of my journey in getting that conviction. The first conversation I had with Riley was when I was still in graduate school. And I remember we were introduced through my brother. They were both going to Dartmouth the time.
Gabe Otte:
And Michael, my brother, gave me a little background on Riley, what he has done, and he was going to drop out to go do the Teal Fellowship. And in that first conversation, I was talking to Riley and Riley told me what he was doing with his current company. And I was sort of like, why the heck are you doing this, right? Why not just go to school like everyone else?
Gabe Otte:
Go learn something before you go and do something else. And it was just so matter of fact in how he responded. It floored me. He just said, well, I probably only have 50 or 60 years left in my life. So I want to make sure that I'm doing something meaningful with those years. This 19 year old kid. And so it, I think shocked me a little bit.
Gabe Otte:
And it made me think about what am I doing with my life? Why am I not doing what I want to be doing? And in that moment, I think there was a realization of a lot of people come up with excuses on why they can't do something. And those excuses are exactly what they are. They are probably fictional narratives that we come up with on why we can't do something.
Gabe Otte:
And Riley was really instrumental in helping me break out of that. Both of us independently came to the conclusion that the key to solving cancer or at least one important key to solving cancer is when we detect a disease. And at the time we weren't detecting the disease early enough for us to cure it. And that's what we wanted to work on.
Josh King:
You began a keynote address at the 2019 Future of Individualized Medicine Conference on this stark difference between the survival rates of those that have localized and metastatic cancers. What are the current rates of diagnoses between the two?
Gabe Otte:
So in most cancer types, when you're talking about the survival rate between when you're detected early versus late, if you detect it in stage one or two, that chance of survival is probably greater than 90% in most cancers. If you detect it in stage three and four, the chance of survival goes down below 10%.
Gabe Otte:
So we're really talking about the difference between life and death when we're talking about the difference between early and late detection. So our focus at Freenome has really been about how do we skew that detection rate? Because today 80% of all the cancers that we detect are in stage three or stage four.
Josh King:
There are other companies, Gabe, that have looked into using blood tests and genomics to find cancer and other diseases. Some of those companies have done so over the past few years achieved a level of infamy as a result of their work. Here is 60 Minutes from last year.
Audio:
Theranos raised nearly $900 million from those investors who now say they were swindled by Elizabeth Holmes and company President Ramesh Sunny Balwani. The pair claimed in investor documents obtained by 60 Minutes, that Theranos technology was validated by the FDA, pharmaceutical companies and was deployed on the battlefield by the US military in Afghanistan. Those claims were fabricated.
Josh King:
Gabe, I listened to you and Riley on the Healthy Dose Podcast where you said that the Theranos implosion had minimal effect both in the field of genomics and also the willingness of investors to support your work. Not even a hiccup as you went along your work?
Gabe Otte:
Yeah, I was actually surprised because I'm hardly asked about Theranos by investors generally speaking. And it's not because they're not trying to give me a hard time or anything along those lines. It's not like they're trying to just ignore that Theranos happened.
Gabe Otte:
It's more that when you build a company intentionally and step by step and you're trying to prove things one step at a time, it looks very different than the way Theranos was built. And there's still a lot of biotech companies out there that are trying to solve these big problems. And some companies are trying to jump to the end and other companies are trying to do this step by step.
Gabe Otte:
The step by step is far less sexy than trying to just jump to the end. But at the same in time, if you're doing it step by step, the investors are going to recognize that they're going to see the evidence that's being built up. And they're going to be able to work with you to help you build the company up to what it can be.
Gabe Otte:
And in fact, I've found that the more sophisticated investors actually value the fact that we've decided to go this long path down to FDA approval to take all these steps to prove out that our techs actually works with peer reviewed publication, with talking at medical conferences.
Gabe Otte:
And they don't think it's actually a negative thing that we're taking multiple years. Company's been around almost five years now and we still have a little ways to go before our product is going to be available to patients out in the market. But it does really take that much time to build something new into a medical field
Josh King:
Step by methodical step, it takes so much time Gabe. Something that we've heard here at the New York Stock Exchange from the biotech company founders in particular, is this difficulty in balancing and running a business with the core research work. And you say you've been at it for five years versus also building a business for the long-term.
Josh King:
Earlier this year, Freenome closed its series B raise of $160 million. We had Andreessen Horowitz's Scott Cooper on the show. And he talked about how in the private market flush with investors, the tables have turned. Entrepreneurs are now looking for more support than just funding.
Josh King:
Is that something you think about when you're building your capital raise and you're going in door to door and sometimes you're getting money, but what you're really looking for is counseling and advice?
Gabe Otte:
Absolutely. And more than that, I would say you're wanting to find the right partners. You have to talk to these people on a regular basis. You have to, at times, have some really tough conversations. Are they going to be okay with that? How do they react to that? This is a long winding road. When things go wrong, how do they react to that?
Gabe Otte:
Do they give you advice or do they chastise you? Maybe a little bit of both is probably a good thing. I think finding those right partners, it's kind of a cliché, but it is really like dating when you're trying to raise money because that chemistry has to be there.
Gabe Otte:
You have to be able to be very open with the person that's sitting across the table from you, the things that are going well and the things that are not going well. And yes, ask for help when things are not going well or even when things are going well. But asking for help is also a very difficult thing if you're not partnered up with the right people.
Gabe Otte:
Andreessen Horowitz I think is a great example of somebody who believed in us from the very beginning and who's given us a lot of support that we needed, especially in the earlier phases of the company when we're trying to hire, when we were trying to get partnerships and no one knew who Freenome was.
Josh King:
If the metaphor for searching for investors is dating, I'm wondering what the metaphor of successful leading and managing is. For one, your compensation structure is tied to something called self awareness. How does that tie into what makes you a better manager, a better leader?
Gabe Otte:
So someone recently asked me this question of if I can boil it all down, all the lessons that I've learned as a co-founder and CEO for the last several years, what would that be? And reflecting on it, the answer to that question was I'm a huge people pleaser. And over the last several years, thankfully, I've become less of a people pleaser than I used to be because you cannot be a people pleaser and be a good leader.
Gabe Otte:
Every decision that you have to make as a CEO is going to disappoint someone. And if you're the type of person who stays up at night because you know that somebody is upset with you, this job is going to kill you. At some point, it was this recognition that you cannot please everyone and you have to sort of go with what is best for the company and not be too emotional about the decisions that you have to make.
Gabe Otte:
That self-awareness, that lesson that I learned about myself was crucial for me to take that next step forward as a leader. And it was an expensive lesson to learn because I was not very self-aware. Like many young people, I was very delusional about a lot of things, what my capabilities were. Definitely overestimated my capabilities.
Gabe Otte:
I like many people would say things like, oh, I just say things the way they are. I love that phrase, because so many people say that. But it's more of, can you actually say what needs to be said in that moment? So in our company, yes, we do value self-awareness because I found out that most interpersonal issues in the workplace happens generally because somebody is not self-aware, somebody is overestimating their abilities, somebody's underestimating other people's abilities.
Gabe Otte:
Somebody is thinking they know the truth when they don't. There are all these issues, but if everyone was a little bit more aware of their strengths and weaknesses in reality, then we can avoid a lot of those mistakes.
Josh King:
If part of your compensation is connected to self-awareness, how is that systemically calculated and reviewed?
Gabe Otte:
I think one of the big things that even I'm learning even to this day is how I'm perceived and how I perceive myself are two very different things at times. And so you have to have a system where you can get a sense of what are the people that are working with a particular employee saying about that person?
Gabe Otte:
And across multiple things, because some things were very self aware and other things were not. And so I think it's unfair to sort of put a single score to an entire human being. But it's really about how software is this person based on what their team members rate them on, say empathy or self-awareness or their job responsibilities, ability to teamwork, all these things and what they rate themselves as?
Gabe Otte:
And you can learn a lot from that delta. And it's interesting because in that quantification, there's never been a surprising thing for me. When I look at people in my company and their scores on that, it's usually just a quantification of what I already sort of feel about that particular person. But it's just nice to see that play out more concretely.
Josh King:
How do you use that data to build your team? For example, why was Jimmy Lin the right person to hire earlier this year as your new chief scientific officer?
Gabe Otte:
As the company develops, you want different people coming in at different times because the skillsets that are needed are very different. When you're early on, early on you want people who are just doing everything that they can to keep the company going. And that can be everything from managing people, but probably primarily just building the thing that you need to build.
Gabe Otte:
I think as the company grows, the people who lead your different departments, they need to be able to lead a group of people across multiple disciplines and move in the same direction. And so I think the amazing thing about Jimmy was here's somebody who's literally given a TED Talk on early cancer detection, who when you meet the guy, there's not a bad bone in his body.
Gabe Otte:
I mean, that guy just cares about everyone that he comes in contact with. He inspires people, not in a contrived way, but in this genuine love for discovering something new and a genuine love for helping patients.
Gabe Otte:
And so at the time, I think as the company was transitioning into becoming a bigger company, we needed somebody who was going to lead all the different science orgs that we have within Freenome with this vision for what we're doing and somebody who can actually remind everyone, why are we here? And why is what we're doing important? And Jimmy was really the right person for that.
Josh King:
I heard in an interview, you did the idea of servant leadership. Who is the leader of servant to? The company, the employees, the board, or someone else?
Gabe Otte:
As a leader, you are a servant to all of the people that you oversee, because if you can't make the people under you successful, then you're not successful as a leader. The challenge of course, is people get this wrong all the time. Servant leadership is not the leader just being nice to everyone. That's not what it is.
Gabe Otte:
Because you still have to get the mission done, make the company successful. Servant leader is somebody who genuinely cares about the people under him or her and does whatever is necessary to make that person successful so that the company as a whole can be successful. And sometimes that means being pretty harsh about things, especially if that person is not being self-aware or if they're underperforming and things like that.
Gabe Otte:
You want to be very upfront with them, but you do want to be empathetic in your approach in the sense that some people are very good with direct feedback. Others are really bad with direct feedback. They will collapse in on themselves like a dying star if you raise your voice at all.
Gabe Otte:
And so a good servant leader also has that recognition of who are you actually sitting across the table from? And if you need to give them negative feedback, what is the best way to do it? So that that person learns, so that that person becomes more successful down the line.
Josh King:
No one less than Pope Francis himself considers himself a servant of all people, not the least of which include the homeless. Let's hear a news clip from a European network back in 2017.
Audio:
A new launderette has been opened specifically for Rome's homeless, is been set up by Pope Francis and is located within a hospital complex not far from the Vatican. The idea is to provide free facilities where people living on the streets can wash, dry and iron their clothes. The Popes Laundry as it's being called is being run by a volunteer Catholic charity.
Audio:
Gisepi has been one of the first to take advantage of the facilities and says it's so important to keep clean so he can maintain his dignity. He's very grateful to the holy father and the charity, which have given this opportunity to homeless people.
Josh King:
Companies like Freenome and CEOs like you can contribute to addressing the global issue of homelessness as well, can't they?
Gabe Otte:
It's interesting because I've been very passionate about the issue of homelessness for many years. And there's just a lot of misinformation about homelessness. For example, the United States, the average age of a homeless person is less than 10 years old. And that's not what we think when we think about homelessness, right?
Gabe Otte:
We think about middle age men sitting on the streets somewhere, right? And I think it's that type of misinformation that really works against us as a society in solving the homeless issues is we forget all the homeless people who are single mothers who are taking care of their children, going from shelter to shelter, who just can't afford to buy houses, who are trying to make ends meet.
Gabe Otte:
And so I'm involved with this particular program that is called YES. It's Youth Equipped to Serve where it's really about taking junior high and high school students on weekend long trips to meet the homeless because we all do this, I know I do this, right? Walk along the street, see a homeless person, avoid eye contact.
Gabe Otte:
Just keep going, right? If you are a person and somebody won't even look at you in the eyes, what does that do to you over time? You will start feeling less than human, right? And this act, we dehumanize the homeless by doing this on a daily basis. And I know because it's awkward and you don't want to have that experience.
Gabe Otte:
And so we have kids growing up today who are also going by default and learn that behavior, who's going to do the same thing. And so YES is really actually focused on taking these kids and getting them to meet the homeless people.
Gabe Otte:
And so one of the programs YES has is you break up into groups of threes and fours and you invite somebody to a meal so that you meet that person for who they are, which is a human being, generally became homeless because they had no infrastructure around them and they had a bad break.
Gabe Otte:
And I think just increasing awareness in the next generation in that way is going to meaningfully change how the next generation sees the homeless. It's really changing that perception that's going to change the issue on a more global scale. And we absolutely do have a responsibility as people who have been granted with a lot of resources and a lot of wealth and power to be able to do as much as we can to solve this problem.
Josh King:
After the break, Gabe Otte, co-founder of Freenome, and I get into the genomics behind his company's ambitious goal to identify and even eradicate cancer by revolutionizing how he test for it and treat the disease. We'll be back right after this. And now a word from Teladoc, NYSC ticker TDOC.
Audio:
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Audio:
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Josh King:
Welcome back. Before the break, Gabe Otte, co-founder of Freenome, and I were discussing his career and how Freenome began. Now we're going to get into what the company's doing right now. Here's a clip from NBC News earlier this year.
NBC News:
Kevin Hayes was just 28 years old when doctors told him he had colorectal cancer.
Audio:
This is not a world that I anticipated or wanted to be a part of.
NBC News:
Hayes is one of a rapidly growing number of young people with colon cancer, a disease that behaves differently than doctors have seen historically
Audio:
The earlier that the cancer develops the less it looks like a standard colon cancer.
Audio:
New research from MD Anderson Cancer Center in Houston finds early onset cancer tends to have certain genetic mutations. Tumors can develop in unusual areas of the colon and they may need to be treated in new ways.
Josh King:
Gabe, Freenome's initial work has been in colorectal cancer. Why start there?
Gabe Otte:
There's a lot of reasons why a technologically functioning test never makes it out into the market. Some of it has to do with whether it's affordable or not, but also some of it has to do with, even if you could detect a particular cancer early, does it actually help the patient at all?
Gabe Otte:
And in many of the cancer types today, even if we detected the disease early, it's not at all clear whether it will help that person be better, right? There are certain cancer types for sure you know if you detect it early, you can save that patient. And colorectal cancer happens to be one of those cancer types because the follow-up step is you go in with a colonoscopy and you go and remove that tumor.
Gabe Otte:
And so it was a very pragmatic decision of what cancer types do we believe we can cure today by early detection because we have a concrete follow-up step to actually go and treat the tumor itself. And colorectal cancer was at the top of that list.
Josh King:
So how is the clinical test set up to make sure you get enough data that you can control for variables like in the example that we just used location, age of the patient, their gender?
Gabe Otte:
It's a tough problem in screening because the types of studies that you have to do is very, very large. For example, in colorectal cancer, the incidence rate in the population say above age 50 is about 0.7 to 0.9%. So it's less than 1% of those patients or those people actually get colorectal cancer, which is good news, because it's still fairly rare into population.
Gabe Otte:
But that means that if you want to show that your test actually works in a population, you have to collect a lot of patient samples that are "healthy" to get to that less than 1% of patients that are actually going to develop colorectal cancer.
Gabe Otte:
So the study that we're running to get to FDA approval is going to be more than 10,000 patients because if you collect over 10,000 patients, that's how you get to barely, hopefully around 100 colorectal cancer patients. And you need between 50 and 100 patients to really show what statistical significance that your test actually works.
Gabe Otte:
And so that's a huge study. It's tens of millions of dollars to run that particular study, but it's not even the toughest cancer. So something like pancreatic cancer, the population incidence is more like 0.1%. That means if you want to get to that 100 patients or so you're going to have to do a minimum of 100,000 patients.
Gabe Otte:
And that study is going to be hundreds of millions of dollars to actually perform. So I think there's really non-trivial barrier to be able to launch this test that really has nothing to do with the technology itself. You just have to prove in the right population that this test actually works. And that is something that takes a long time and takes a lot of money.
Josh King:
Proving whether the test actually works, how effective are the current tests and what is the improvement that you're seeing with Freenome's blood tests?
Gabe Otte:
So the issue, for example, with colorectal cancer is not that the existing tests don't work. In fact, a colonoscopy works really well. It's got accuracy greater than 90%, obviously because you're actually going in there and looking. The problem is of the people that are told by their doctors to go and get a colonoscopy, less than half the people actually do it.
Gabe Otte:
It is a non trivial procedure. It is very uncomfortable to prep yourself to do and it takes an entire day, right? Maybe more out of your schedule, right? Because you have to go and get it done. And most people are really busy and they don't want to go the difficult prep procedures. And so the idea of bringing a blood test for early detection of colorectal cancer is to make screening as accessible as possible for patients so that we can eradicate cancer.
Gabe Otte:
Truth be told, if everyone that are told by their doctors to go and colonoscopy actually does it, we will probably cure colorectal cancer tomorrow or at least a vast majority of those cases. But as the clip from NBC just told us, the colorectal cancer is also happening in younger and younger populations.
Gabe Otte:
And so we just need to make something that is cost effective, that is easy for people to take on a broad scale so that we can get everyone's screened for colorectal cancer.
Josh King:
So if you were looking to identify the cancer before the tumor is substantial, before some of the things that you might find in a colonoscopy, what are your tests specifically looking for?
Gabe Otte:
When the tumor forms in your body, there's a couple of things that happens. First, the immune system is trying to go and attack the tumor. As the tumor gets larger and larger, the immune system fails and it dies. And when a cell dies in your body, it spews use out everything that's inside of it, including the DNA, the RNA and the proteins.
Gabe Otte:
The same thing happens with the tumor. When the tumor forms, the tumor cells also are rapidly growing and some of them will die and spew out their DNA, RNA, and proteins into the blood. It's the DNA, RNA, proteins from the immune system that's trying to attack the tumor and the tumor itself that we're detecting in the blood as an indication of whether the tumor exists and whether the immune system is reacting as if there is a tumor in your body.
Gabe Otte:
And those two signatures combined gives us the power to be able to detect just from a blood sample, whether your body is currently dealing with a tumor or not.
Josh King:
I mean, how are you able to correlate between the immune response and a localized cancerous tumor?
Gabe Otte:
So obviously there are signatures, as we talked about earlier. There are different signatures that are being expressed from the DNA depending on which cell type you're dealing with, right? They all have the same DNA, but the different genes are being turned on and off. And you can detect the same thing.
Gabe Otte:
If you have a tumor in your colon and your colon cells are dying, you can detect that it's actually got signatures that's from the colon tissue. And you'll be able to find that disease in a localized manner.
Josh King:
Have you been able to leverage machine learning to assist in the normalization of data as you've been doing this work?
Gabe Otte:
So there's a myth about machine learning out there that this is some scary black box that you throw data in there and something comes out on the other end. That's not what machine learning is at all, right. Machine learning at its core is just a computer doing statistics.
Gabe Otte:
And so if we remember back in school, we remembered a bell curve and then we sort of draw a line somewhere along the bell curve and say, the people that fall on one side is this, people that fall on the other side of that line is this, right? Machine learning is just basically doing that, drawing that line just on a higher dimensional data.
Gabe Otte:
So more than three dimensions and you're trying to take all these parameters in. And so when you are dealing with so many different signatures like the DNA, RNA, proteins, and they're all a little bit different and they all contribute different aspects of biology, where do you draw that line? Where do you draw the line so that you say, oh, if the DNA, RNA, proteins look like this, you have cancer?
Gabe Otte:
As opposed to, if they look like that, then you don't have cancer. And that's what we use machine learning to help with just because human beings are really good at drawing lines in two dimensions, but beyond two dimensions, it's pretty hard to sort of know what that actually looks like. And that's where the machine learning comes in.
Josh King:
Are you solving the technical challenges of the size of these immense datasets with a hardware or a software solution?
Gabe Otte:
So obviously, Google is one of our investors. They know a thing or two about how to store and play with big data and make it useful. So we have learned a lot from them being on their platform. At some point, the storage of the data also becomes a problem because it's a tremendous amount of data per patient, right?
Gabe Otte:
You can generate upwards of 50 to 100 gigabytes of data per patient. And so just being able to ingest that data, store it, and then make that data redundant so that you don't lose it if a server goes down. That in and of itself is a technological challenge. Then the second part is even more complicated of how do you take that 50 gigabytes of data and actually make a test with it?
Gabe Otte:
And that's required new tools that we had to develop, new analysis tools that we had to develop because there's not a lot of analysis tools that can handle that much data. And so we've had to sort of innovate on all sorts of these fronts with our partners to be able to even just do the basic things that we have to do with our data.
Josh King:
The learning aspect of the machine learning suggests that you expect your tests to become more accurate over time as the machine ingests additional datasets. Is that localized the individual cancer tests, or does your platform allow the potential for information gleaned from all of your colorectal cancer patients to inform how it understands cancer in general?
Josh King:
You talked about all the data that one patient will take up on the server plus the backup server. What about this whole population?
Gabe Otte:
Yeah, the hope is that as we get more data from more patients, we understand cancer as a whole better. Some of the patients that we screen might not have colorectal cancer, but might have another cancer type. And we are generating data from that patient. So we will learn a thing or two about what that cancer type actually looks like.
Gabe Otte:
And so the hope is that over time as we get more data, we'll have a better idea of what your blood looks like when you form a tumor anywhere in your body, so that our tests can inform and save many more lives beyond just the colorectal cancer patients.
Josh King:
How do you take all the information that you're able to glean from the blood test to develop like one yes or no diagnosis of cancer? Sometimes you collect all this data. The doctor looks at the patient in the eye and says you have a 57% chance of developing colorectal cancer. And that's a difficult thing for a patient to ingest. What about the other 43% that says I'm going to be fine?
Gabe Otte:
So let's be clear here. While our test is built on the foundation of genomics, it is not a genomics test that sort of gives you based on the mutations that you have, you have X percentage chance of developing colorectal cancer sometime in your life.
Gabe Otte:
What we're doing is a little bit different. We're looking at which cells are dying and contributing DNA, RNA, proteins into your blood. And we're taking that signature and informing you whether you have a tumor right now or not. So that's a very easy thing to confirm. You go and get a colonoscopy as a next step.
Gabe Otte:
And if you have it, then they will go and excise the tumor from there. And so our hope is to not play that percentage game at all, because as you pointed out, it's hard to know what, for people, what to do with that information.
Gabe Otte:
We don't think that's particularly helpful for what we're trying to do. We need to be able to take that blood sample and be able to tell you, do you have a tumor right now or not? So that you can actually go and do something about it.
Josh King:
As we wrap up, Gabe, last month Freenome announced a partnership with ADC Therapeutics to use your platform to identify biomarkers that correlate with clinical response to ADCT-402. This is going to help ADC Therapeutics identify what patients would be best suited by the treatment. What does this partnership mean for patients and for Freenome's business model?
Gabe Otte:
Early detection alone isn't going to cure cancer, right? Because we have to find it early and then we have to treat it. That means that the way Freenome can help in this respect is do the early detection, yes, but also be able to point that patient to that next step.
Gabe Otte:
So in the case of colorectal cancer, that next step is a colonoscopy, but in other cancer types, that next step is something different. Whether it's taking a drug, whether it's chemotherapy, whether it's radiation. And one of the things that is really important to just keep in mind is we're all individuals and therefore we're going to react to different drugs differently.
Gabe Otte:
Some people are going to respond to those drugs and other people are not. Right now, for most drugs out there we don't have a good way of detecting whether you're going to respond to a particular therapeutic or not. And so Freenome is partnering up with therapeutics companies like ADC to start mapping out based on the signatures that we're able to capture into blood, which therapies are the patients likely to respond to the most.
Gabe Otte:
So that in the future, you come and take the Freenome test. We tell you whether or not you have cancer right then and there. And then based on your unique profiles, which drug are you most likely going to respond to so that we can actually cure you of the disease? That's really the vision for Freenome's future.
Gabe Otte:
And we will do that early detection in-house with Freenome, but with all the other therapeutics companies out there, making sure we partner up with them so that we can gain an understanding of what in our blood can tell us about whether or not you're going to respond to a particular therapy so that we can essentially marry early detection with early intervention.
Josh King:
I just had my three times a year hygenists appointment, got my teeth cleaned at my dentist, Gabe. Stepping back to look at how genomics can one day fit into the larger healthcare system, a couple of years ago, you appeared on a session with Jeff Kattats at Q and he used the differences between the United States' dental and medical systems to suggest a way that genomics could be used in a positive feedback loop, not unlike my last dental appointment.
Josh King:
Are you seeing any adoption in this country or elsewhere that follows this model of regular genomic assessments?
Gabe Otte:
I think more people are getting their genome sequence, and that's a very good thing because it gives you a foundation of information on who you are. Now, there's a difference between what we call germline mutations and somatic mutations. Germline is mutations that you're born with that's in every cell of your body.
Gabe Otte:
Somatic are the mutations that you accumulate throughout your lifetime, right? Most of the genomic sequencing that people are doing today is really getting at the germline mutations, what you're born with. I think what Freenome is detecting is more on the somatic side, right? What's in your blood right now? How have you accumulated different signatures?
Gabe Otte:
I think as we go forward, people are going to realize germline alone isn't sufficient. So we have to get tested on a regular basis to see how things are changing in our bodies. And we have to give people sort of very specific information on the actions that they're taking and how to actually avoid getting some of these diseases.
Gabe Otte:
Right now, I think the problem with getting tested on a regular basis is people don't really see the utility of it. They don't really know, what does this information actually get me? And how do I... What do I do differently based on that information?
Gabe Otte:
I think as companies like Freenome gain more of an understanding of how your body develops cancers for example, we're going to be able to give patients that information as we detect it really early of, what are the concrete actions that you can take that will allow you to better your chances of avoiding these diseases entirely? And that's a future that's really exciting for us.
Josh King:
Avoiding these diseases entirely. We will be keeping a close watch on Freenome. Thanks so much for joining us Inside the ICE House.
Gabe Otte:
Thank you for having me.
Josh King:
That's our conversation for this week. Our guest was Gabe Otte, co-founder and CEO of Freenome. If you like what you heard, please rate us on iTunes so other folks know where to find us. And if you've got a comment or a question that you'd like one of our experts to tackle on a future show, email us at [email protected] or tweet at us @Icehousepodcast.
Josh King:
Our show was produced by Pete Ash and Theresa DeLuca, with production assistance from Ken Abel and Ian Wolf. I'm Josh King, your host, signing off in the library of the New York Stock Exchange. Thanks for listening. Talk to you next week.
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Outro:
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