Recently, I had the honor of interviewing Robin Smith, CEO of ORIG3N, a company which has created the world’s largest blood cell repository. ORIG3N is using these blood cells to produce patient-specific induced pluripotent stem cells (iPSCs), allowing the cells to be ever-renewing and giving rise to a living database of humanity known as LifeCapsule.
The company also has two other business segments, called LifeProfile and LifeSystems. In this interview, we explore the beginnings of ORIG3N, as well as its creation of the world’s largest blood cell repository, genetic testing business, and future trajectory as a company.
Interview with Robin Smith, CEO of ORIG3N
Cade Hildreth: What inspired you to start ORIG3N?
Robin Smith: That is a great question, because I have an unusual background and history. My father was in the Air Force, and I was born in Korea. My mother is Korean and my father is American, so every three years of my life I ended up moving to a new place and having to learn new things and meet new people. When you have that background, the life of an entrepreneur is not much different.
I sold my last company to PerkinElmer and thought that would kind of be it. It was a tremendous opportunity to drive large scale innovation with a storied American research firm. At that time, I was working at PerkinElmer and was heading up their R&D group, and then my father got diagnosed with lung cancer. Because I was in a military family, I grew up in a different socioeconomic class than I am now. Today, I live in Boston, run a biotech company, and live downtown. I have a different lifestyle than my family when I was growing up, who now live in eastern North Carolina. When I went down to spent time with my dad at the hospital, I felt like I had walked into 1940 or 1950.
The medical technologies available to people in rural America are shockingly behind. I spent the better part of a year-and-a-half going to these type of hospitals with my dad and was mortified at the whole process. It made me recognize how badly we need to disrupt medicine.
When Kate Blanchard and I started ORIG3N, we did not yet know what the end technology was going to be. Nonetheless, we said let’s go license groundbreaking technology that is almost ready to be industrialized. We found iPS cells and identified that they had not yet been industrialized professionally or in a scalable way.
That is the genesis of how we started ORIG3N. I keep thinking, how do we change the treatment and health care available to people in eastern North Carolina, or rural America, or Africa, or South America? Access to regenerative medicine technology should be available to all and we need to facilitate that goal.
Cade Hildreth: When you were starting ORIG3N, how did you secure patent rights to induced pluripotent stem cell (iPS cell) technology?
Robin Smith: It is odd, because you see iPS cells in the news and everyone seems to have a claim to it. When we started, we went from university to university, tracing the technology and asking, “Do you really own it? Who owns it? Who else has rights?”
We ended up circling all the way back to Dr. Shinya Yamanaka’s Team at Kyoto and then reached out to a group called IPS Academia Japan, whose sole purpose is to license Shinya Yamanaka’s technology to people who want to work on the iPSC front.
We called them before we had a lab and said, “Could we talk to you about negotiating a license for this technology?” They said, “Sure, where is your lab?” We said, “We do not have a lab.” They said, “What’s your company?” We said, “We don’t own a company yet, but we wanted to call you first, because we are not going to build a company in this space if we cannot license the technology.” It was an interesting conversation.
I have worked with a lot of companies globally and have great respect for the invention process, so it was good to be able to go directly to the source, the researcher who discovered iPS cells himself. We worked out a very nice licensing agreement with them, and IPS Academia Japan has been a fantastic supporter of ORIG3N.
Cade Hildreth: ORIG3N has three business units. Can you speak to each these and their role within your company?
Robin Smith: Yes, ORIG3N currently has three business units, which are: LifeCapsule, LifeSystems, and LifeProfile. Our repository of iPS cells are ever-renewing and give rise to a living database of humanity we call LifeCapsule. This biorepository is used to create LifeSystems cellular models available to help researchers accelerate the development of safer and more effective drugs.
Next, we want to take LifeSystems to the next level using our HLA-matched cell bank to support the development of iPS cell-derived therapies. LifeSystems will take an evolutionary step this year to start using our matched cell lines. It will probably take us a year to make sure these cells are fully characterized, disease free, and have expected behaviors for expansion. We need to test for those attributes first.
For LifeProfile, people that donate blood to ORIG3N often ask us to tell them something about themselves, so we built our genetic profiling business to meet that request and worked hard to make the price accessible. For our first genetic kit, the Super Hero Test Kit, we charge $19 dollars for it at events that we attend to collect blood samples, like Comic Cons.
It is a great way to get parents and children exposed to genetics. It allows people to learn if they have strong bones or fast muscles or language learning skills. Those are not scary attributes to find out, and our test kits are often the first time people are exposed to genetics outside of a doctor’s office. Because part of ORIG3N’s goal is to democratize access to science technology and educate people, we are trying to make these tests available to everyone.
Cade Hildreth: Do you offer that $19 Super Hero Kit outside of events ORIG3N attends?
Robin Smith: Yes, we sell it for $29 online through our website and through Amazon. We also have a Nutritional Test Kit that is a little more expensive ($150), because it is more complex, and we have a Fitness Test and a Skin Assessment Test.
We also have a Bliss DNA Test that we are about to launch. The Bliss DNA Test identifies how a person reacts to opiates, pain tolerance, various narcotics, and their tendencies for risk-taking behaviors. Another kit that we are going to launch soon is called Bloom. Bloom and Bliss will launch together at a Consumer Electronics Show. Bloom is all about early childhood development, because it can assess music learning genes, identify long cilia within the ears that can help with perfect pitch, cavity propensity, resistance to certain viruses and assess attributes of other genes related to development.
Importantly, our genetic testing business, LifeProfile, helps ORIG3N cut down on the “run costs” related to LifeCapsule, our cell repository. That has helped us substantially, because we have to think, “How can ORIG3N be a sustainable entity that will be around to be responsible custodians of our valuable biological assets?”
Cade Hildreth: How do you view other players within the genetic testing market?
Robin Smith: No genetic kits are mutually exclusive from each other. We do not do ancestry kits, so we are very different than 23andMe. Our customers are their customers and their customers are ours. We believe that the more we educate the populous about genetics the more this market will grow for us and our peers. Our next project is to turn LifeSystems into something that is useful for people in regenerative medicine. That’s our next investment to pursue.
Cade Hildreth: Recently, you announced that you executed genetic testing in 48 hours for attendees of the XMed event. Is that correct?
Robin Smith: Yes, that is right. We made genetic profile data available to conference attendees live during the event. That was cool, because nobody had tried to do it before, and I don’t think any other DNA testing company can actually do it, especially with such a large volume of samples. The reason why we could accomplish it, is that we have developed and integrated automation and software systems that allow us to rapidly extract DNA samples. Part of it was leveraging the DNA technology that we are using for this HLA project that we did, because the volume of cells that we were processing was massive.
Knowing that we had this technology, we decided to approach the people at Singularity and see if we could do genetic profiling for their upcoming XMed event. Daniel Kraft looked at it like, “There is no way you are going to pull this off. You are going to be really publicly embarrassed if it doesn’t work.”
We said, “We know.” We were willing to take that shot and not be scared to do it. The good news is that the Singularity community was absolutely blown away that genetic testing could be done that rapidly, and it has led to several other business opportunities. We really appreciate Dr. Kraft’s support and owe a lot to Singularity for giving us a shot at this experiment.
Cade Hildreth: Recently, ORIG3N announced it had identified Superdonor matches for 90% of the U.S. population. How would you define Superdonors and how did that discovery within ORIG3N’s LifeCapsule bank occur?
Robin Smith: What we look for in Superdonors is more complex than the standardly defined tissue matching process. We test for up to nine different major sites for the allogeneic matches. Most Superdonors are defined as A, B, and DRB, which are three major sites. We do look at those standard sites, but we also go a bit deeper. We have dozens of our samples that are homozygous at more than six of those sites, and we have some donors in our bank who are homozygous at more than nine of those sites.
We have been doing high-throughput DNA extraction and cell processing in our facility, but LabCorp, our partner and our investor, has been doing the actual HLA identification component in their laboratories. They have the infrastructure to do that on a huge scale.
Cade Hildreth: What was the process of identifying Superdonors within ORIG3N’s cell repository?
Robin Smith: What happened was we first collected all the samples and had them in our repository. There are HLA haplotypes that are most common in the population based on U.S. or European or any other ethnic background. We said, “Ok, this is the code or nomenclature for an HLA match for 5% of the population, then let’s see if we have that code or that match is in our database.”
This caused us to embark on what we jokingly called in our lab the “Manhattan project,” because we realized it was going to take a really long time.” Of course, we could not actually call it the “Manhattan project,” because ORIG3N is located in a different place and at a different time. Nonetheless, we wanted to name it after a place and we were standing right outside by a sign that said Black Falcon Drive, and we instantly knew that “Project Black Falcon” was it.
That is how the project was named Project Black Falcon, the project of extracting DNA from every single cell that is in our repository, one by one.
It is a Herculean effort to just get the DNA out all those cells, and then we need to lay them out and have software that actually maps them on plates. We were interested in a commercial partner, so we started pricing it with vendors who were charging $300 per match. After multiplying the numbers, we realized that this approach would make it an $80-100 million project.
Alternatively, we could build the platforms ourselves. Knowing this, we had a conversation with our partner LapCorp and teamed up with them to make it economically feasible to use their facilities to support Project Black Falcon. Today, we send extracted DNA samples to them. They do the sequencing, sift through the data, and send all the raw data back to us in datafiles that we import into our databases.
We then try to match this data against datasets that are stored in publicly available data donor registries of population cohorts. With that process, it has been rinse and repeat, over and over and over every week, for the past six months or so. Every once in a while we would get a hit.
Remember, for the haplotype matches that exist, whether they match 4%, 6%, or 3% of the population, what we are looking for are homozygous matches. These are very unusual in the population. On chromosomes, you get one set from your mom and one from your dad. For example, if your numbers are 01 for the A and 03 for the B, that means you need to have 01, 01 (both of your chromosomes have to match). It cannot be 01 and 16 and 03 and 45. It has to be 01, 01 and 03, 03. You must be homozygous on each site.
When we are looking at nine sites, that means somebody has inherited the same haplotype across all sites, which is an extremely rare thing.
We joke that we should create a dating app, because human beings are attracted to each other based on how diverse their haplotype antigens are on their cells. Somehow, humans evolved to find opposites HLA matches, so that we keep mixing them within the population. Consequently, finding homozygous HLA matches are rare cases within our database. They are needles in a haystack.
Cade Hildreth: Wow, that is a fascinating backstory. Are you able to speak about how many units you have in the cell repository?
Robin Smith: We don’t talk about exact numbers for blood samples, but on any given day we process up to 1,500 to 2,000 blood samples and we have been working for about three years. You can work the math out. Some days, it might be lower, like several hundred, but it is an incredible batch of samples.
Cade Hildreth: When did the partnership with LabCorp start?
Robin Smith: It started about a year and a half after we were founded. When Kate Blanchard and I started this, we were funding the lab ourselves. When we went out to raise our first round of financing, we got back in touch with our old investors who had helped sponsor my previous companies. They introduced us to LabCorp, and LabCorp had taken a look at two of my previous companies, but those companies were a little outside of their comfort zone, because they were software businesses built around life science.
With ORIG3N using iPS cells as potential diagnostic tools, the amount of diagnostic analysis that we were going to have to do with our cells intrigued them, and they identified it as a really nice match. As a result, they came in on our very first round of financing, a Series 1, and invested alongside the rest of our investors. Then, in our proper Series A round, which was closed less than a year after that first series of funding, LabCorp came in again. At that time, Tom McMahon, the founder of LabCorp, personally invested and then joined our board as well. That relationship has been building as we have been going.
We also have an agreement with LabCorp where they are doing backup cell storage for us, so they have given us a lot of assistance for scale-up and fast growth. It is also fantastic to have a “big brother” around who has done this many times to say, “Here are the pitfalls, here is some guidance where you should be a little bit more careful, or a little bit more thoughtful.” It important to have that kind of support behind us.
Cade Hildreth: That is an incredibly synergistic relationship. How was your relationship to the LifeCapsule project evolved as the size and scope of it expanded over the past few years?
Robin Smith: It was a fascinating process for us to watch LifeCapsule grow from what was initially a cool asset for us use to facilitate R&D, into suddenly getting big, and then huge. Over time, LifeCapsule also started holding these biological “keys,” the HLA matches within it. That really changed our thinking, because suddenly we were not only the company building this repository, but the custodians of a valuable biological asset.
That is a different way to think, because these cells are immortal and they are frozen forever and they are going to be around forever.” We have to take care of these valuable biological assets, and that makes us think very differently about how we approach the business.
Cade Hildreth: That is profound. I love the phrase, “custodians of these assets.” When I explored your partnership with LabCorp for analyzing ORIG3N’s blood samples, it mentions that LabCorp is exploring steps for a clinical program next year. What will that entail?
Robin Smith: Yes, it is important for us to validate our cells to ensure that they are disease and virus-free and make sure the cell lines are as close to perfect as we can get them. That is one of the key aspects we are aiming to accomplish. Once we have that achieved, the big question is, “What are we going to do next? What are we going to do with these cells?
Within universities in Japan, there are researchers that are rather far along with using matched tissues or even iPS cells for therapeutic purposes. What we thought we would try to do next year was start initiating some early, early stage safety programs around a single one of our lines as a safety test to see if it is actually safe and has potential as a therapeutic, or at least safe as an ex vivo diagnostic that would allow “out of the body tissues” to be generated for drug efficacy screening. Nobody has done this on an industrial scale in the United States, so we are still trying to figure out, “How do we approach that problem and do it the right way, using our LifeCapsule bank as a catalyst platform?”
We are also investigating how to partner with companies that may need to use these cells and matched tissues for their programs. Again, as we think about being custodians of these biological assets, it is not feasible for us to pursue all possible applications, so we want to make our cells available to others to accelerate new applications. So that is another angle of how we are thinking. How do we get our platform out there so that it is available for use from all, from academic to industrial groups?
Cade Hildreth: What do you expect for ORIG3N over the next 5-10 years?
Robin Smith: Great question, because I spend every waking moment thinking about how we grow our company, build the business, stay alive to see that 10- year time frame, and be good custodians of our valuable assets.
I think ten years from now it will be like when people first started using internet in 1993. At that time, people thought the internet came out nowhere and were both awed and shocked. Today, regenerative medicine is like the internet was in 1993. I believe we are about six to nine years away from that world where people will be building applications using regenerative medicine technologies to help heal people and allow them live healthier lives.
When you look at your iPhone or your smartphone now, it is hard to imagine that in 2007, there were no iPhones around. In the same way, there will be a point in the near future when someone will to walk in say, “What do you mean you have a broken spine? What do you mean you’re paralyzed? What do you mean you have a damaged heart after a heart attack?”
To people 10 to 15 years from now, those concepts of disease and injury will be as alien as not being able to have a smartphone today. I am really confident this is going to happen. Therefore, we are figuring out how we do build a platform that will enable it to happen as fast as possible. We are not directly thinking about the applications, because those are always going change.
Here is another analogy: It is like we are driving across the country at night and we have our headlights on and can only see 200 feet in front of us. We are driving 80 miles per hour and know there is a West Coast out there, even though we cannot see it. We are constantly turning the wheel a little to the left, a little to the right, slightly changing the steering wheel, because the steering represents the regenerative medicine applications that we are now passing by
The goal is regenerative medicine, the future that we cannot see yet, but that we know is out there.
Part of our goal is, how we do start that drive? How do we undertake that road trip? How do we keep modulating, learning, and adjusting as we go?
Cade Hildreth: If you could summarize how you would like to be viewed as a company in one or two sentences, what would it be?
Robin Smith: Wow, that’s a really good question. It is so complex that we struggle with that answer. Most importantly, we want to be known for is being custodians of our first of a kind asset to exist on planet Earth. We also want to be a platform from which regenerative medicine can spring board. Now that we have identified HLA matches within our cell repository, we have taken the first leap toward being that platform.
Those two goals are intimately related, because you cannot create a regenerative medicine platform, if you are not thinking about the future of these technologies in ways that are thoughtful, careful, and ethical