Developing Therapies For Autism And Making Scientists More Translational With Dr. Mark Tepper
In this episode, Scott Wagers chats with Dr. Mark Tepper, CEO of EuMentis Therapeutics and a seasoned innovator in life science and healthcare. The discussion ranges from the difficulties of developing therapies for autism to making basic scientists more translational. Mark opens up about his personal philosophy of getting through the many challenges of medical research and entrepreneurship. He also shares insights on guiding medical teams on performing in a more productive and collaborative way, leading to creative outputs that could stand the test of time.
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Developing Therapies For Autism And Making Scientists More Translational With Dr. Mark Tepper
In this episode, I have a discussion with Dr. Mark Tepper. He's had many years of experience in the biotechnology and pharmaceutical industry. He has led drug discovery and drug development programs that span a wide range of therapeutic areas, including oncology, immunology, rheumatology, endocrinology, metabolic diseases, central nervous system disorders, inflammation, and pain.
Following a fifteen-year career in large pharma research and development, in 2002, he left large pharma to become a serial entrepreneur where he founded multiple successful biotech companies. In the last few years, he's raised over $200 million in capital for his ventures. He's taken two of his companies public and sold another. If you know anything when you have one company going public, that's quite successful. He got three.
He is someone who knows how to go beyond publications. As you can imagine from his resumé, he has lots of insights to share. We talk about how to get teams to think more translational and how to get them to perform. We go into the difficulties and one of his current passions, which is developing therapies for autism. We even touch base on his personal philosophy that helps him get through the myriad of challenges that comes with being an innovator in the medical field.
Scott, thank you for the opportunity to do this with you. I'm excited about it. My name is Mark Tepper. I'm currently the CEO of EuMentis Therapeutics. It is a company focused on pediatric neurodevelopmental conditions, autism, Tourette syndrome, and others. I've been in the biotech industry for many years. Half of that was in large pharma companies at Bristol Myers and Serono. They both are multinational companies.
The other half of my career since 2002 has been as a serial entrepreneur starting biotech companies based on novel technology, focused on developing therapeutics. My companies develop therapeutics. I'm agnostic at this point in my career to the particular disease, the therapeutic area. I've worked in many immunology, oncology, pain, neuroscience, and reproductive biology, which is where I got my PhD in. What excites me is simply finding an asset or an approach that can be used to develop a medicine that will solve an unmet medical need.
It’s great to have you on. I'm so happy you took the time because learning all that you told us, there's a lot we could go into and a lot people can learn from. As you said, you have a long record in the field and doing stuff that is beyond publications. Bringing things to market and making them happen is important. Before we dive into all that, I wanted to take a moment to say, is there something on your desk or in your environment around you that you could describe for the audience?
That's meaningful to me?
Yeah.
I keep on my desk a small marble replica of the Colosseum in Rome. I keep it there for a particular reason. When I worked for Serono, it was a Swiss-based company, but they had sites all over Europe and the US. I, at one point, ran their US site. They had sites in France, Switzerland, the UK, Italy, and Israel. I ran a global project for a while there besides being part of management.
I had a team. The immediate team was about fourteen people, but the resources under those fourteen people on the project at some point represented over 100. Since I was the only American on the team, I took many trips to Europe. We typically have our project team meetings there. They'd come here now and then, but more often, I would go there.
I've been to Italy and particularly Rome probably over a dozen times. The first time I went to Rome for Serono, I think I took an extra day or two. I walked around Rome for miles and miles and visited all the sites, from the Pantheon to the Colosseum to the Vatican. Over time, for each of our project team meetings, we would make a special effort to take at least half a day and take the whole team and do something different.
One time, we had one of the team members who knew somebody who was a tour guide for the Catacombs of Rome. He was able to take us. Not that many tourists go down into the catacombs. I don't know if you need special permission. He took us not only into the catacombs but also into the lower levels of the Colosseum. It's hard to get an image of the catacombs that you can keep on your desk and have the meeting. I ended up getting this replica of the Colosseum.
What it represents to me is the multinational nature at that time of Serono, but of what developing drugs for people, for humans, is about. It doesn't have borders. The Colosseum has a long history, but the Colosseum, to me, is this symbol of an early time that took a lot of effort to build and in some sense, it's a technological masterpiece. I felt that it was what we were building with the team. I love to look at this not only because of the beauty of the structure itself but of the meaning of that. Every time I look at it, it brings back fond memories to me of that team and of the multicultural effort that makes a difference.
Why do you think that makes a difference? Maybe you compare it to other ones that have not been multinational or multicultural. Why do you think that matters so much to the innovation process?
First of all, at a philosophical level, the human condition doesn't differ by ethnicity or territory. There are different political ideas, but the human condition itself is. I think that's important. In the case of discovery, what is it? You have an idea and you have to pursue that idea. Even when you get a grasp early on of some potential therapeutic, whether it's a protein or a small molecule, you need so many different disciplines to bring it forward and advance it ultimately to a commercial product.
At a philosophical level, the human condition doesn't differ by ethnicity or territory.
You can do that within one culture, but everybody has their expertise. We had teams with expertise all over the world that had different expertise. In Israel, there was a site called InterPharm that specialized in growing mammalian cells or making recombinant proteins. In Italy, in Pomezia, just outside of Rome, there was a site that specialized in all of the analytical work and other work involved in advancing the program.
It’s having different viewpoints from people. Technically, they may be equally capable across the globe, but having different viewpoints and different cultures as part of a project, ultimately, you're not solving a problem that's unique to any one country in the therapeutic space. You're solving medical issues that are worldwide. I think it brings so much more diversity to solving the problem, both technically and intellectually.
I was listening to a podcast with Greg Wolfram, who writes WolframAlpha, which is a computational language for everything. The discussion was about the fact that when you look at languages, there are some things you can't necessarily describe or translate between languages. The question becomes, “Can you ever express that across that board?”
In a way, maybe that multicultureness is where you have some advantage there because they have a different perspective. However, you can't even talk about that in English because, in Italian, that's the only perspective there is. They can only express it to you, but maybe that's a bit of a stretch. That's potentially what you're describing there, I think.
Absolutely. In Italy in particular, but in Europe in general. People tend to eat later. The dinner meal has a different meaning. It becomes more of a social activity in my experience in Europe than it is in the US. There's some of that here in the US, but women tend to participate more. I can remember team dinners that we'd have before dinner, an aperitif. We'd get together and have a cocktail hour.
You have cocktail hours in the US, but it's much different there. You go through the dinner and then after dinner, there's typically an after-dinner drink or whatever. The women participate in that. Here in the US, it tends to be more men. I think all of that contributes to trust, camaraderie, and communication. Let's face it. At the end of the day, it's communication that makes the difference. To me, that's what I enjoyed most about those multicultural activities. I've been all over the world. Since then, I've been to China, Japan, and Southeast Asia. I haven't had the privilege of getting to Australia yet, but all over Europe. That diversity of culture adds so much to the team effort.
One thing that's always struck me and I don't know if you've ever been to Oxford or Cambridge. I was in a meeting with a person who was a lecturer at Oxford. He was describing how they have a high table. If you're a professor there, you can go there and eat at a high table. It’s really good food and drink, but that's part of the process of learning.
For example, J.R.R. Tolkien, there's a pub in Oxford where he sat and wrote the Lord of the Rings and all this kind of stuff. There's something about that helps loosen people up and build trust, as you said. I think that's a very important aspect and maybe that's a tip to take. Don't pass up on the good food, wine, and after-dinner drinks.
It's a very important aspect. Part of it is work-related, but part of it is multicultural communication. It opens up your thinking to different ways of doing things. In the UK, along the lines of what you're talking about, if you go at 5:00 or 6:00 or even 4:00 sometimes, you have these pubs that open up out to the street. In America, you're not allowed to do that.
The pubs become the center of social activity. I think Americans spend too much time focused exclusively on work. If the work isn't producing an outcome that's quantifiable, they don't want to do it. In Europe and other parts of the world, there's so much value put on social interaction and I think that translates very much to not only quality of life but to quality of work. You need to trust and rely on other people. The more you appreciate their cultural uniqueness, the better you can relate and the more engaged you can get with these people.
Therapies For Autism: In Europe, there is so much value put on social interaction, which translates very much to quality of life and even quality of work.
One concept that I've been thinking about a lot lately relates to that. It's the idea of social capital. If you have financial capital, you're building up social capital there, and that's useful to come back and use that to apply it to do what you need to get done.
In this time of COVID, in the last few years, social capital has been impeded significantly and that's why social media has become so prevalent and important. The problem with social media is that you don't know what's real and what's not. If I'm talking to you, most people you talk to aren't telling you lies, but there's something about being behind the screen on social media that allows people to say things that may or may not be true. I think that, to some extent, diminishes the value. It makes social media not the equivalent of face-to-face.
It is hard to verify facts in social media. There's something about being behind the screen that allows people to say things even without proper basis.
That's a great perspective on that. Let me shift a bit because I think that was a great way to bridge across from a marble statue into some great ideas about how to work together. What excites you the most about what you're doing currently?
My company, as I said, is focused on these neurodevelopmental conditions. These are tough conditions to treat. By nature alone, they're heterogeneous. Autism is a spectrum. It's not a single condition. Even some of the other ones, like Tourette syndrome. It varies greatly. There's a high unmet need, that's first of all. Second of all, these are conditions of children in a developmental stage.
The impact of these conditions isn't simply the impact that they have while the children are developing. They last with them all their lives. I don't mean only biologically. I mean psychologically. Let's take autism. These kids have a difficult time interpreting social interaction. They may have problems learning. Many of them do. They get ostracized. Nowadays, the tendency is to mainstream them and there are real advantages to mainstreaming, but there are disadvantages too. These kids get picked on.
If you treat cancer, let's say, if you get rid of that cancer, that person's always going to remember they had cancer, but they're cured. There are no cures here, especially if you don't have a treatment for these diseases, either of them. Tourette and autism have no current standard of care or current therapy-approved therapy. Making a difference in these kids' lives to me is very rewarding. That's specifically what I'm doing now in terms of the process, which is what I've done my entire career, which is to discover and develop drugs.
First of all, the joy of doing that is bringing something or translating something from the earliest phase of discovery to an idea. Maybe some data in an animal to humans. I remember the days when we took a new molecule first into humans. That's the first patient dosed. We would all be holding our breath because you never know. Is it going to be safe? Is it going to have adverse events? Are they going to be serious? Being able to see the development of something brand new that can make such a difference in patients' lives and their families lives potentially to me is what I love about what I do.
You said there is no treatment for neurodevelopmental disease and maybe some stuff for neurodegenerative coming on the horizon. What do you think the future is going to be? How do you see that unfolding?
Unfortunately, I think the future is going to take a long time to get to where we want to be, where we have effective therapeutics. You may have seen there was an announcement of a Lilly antibody for Alzheimer's against soluble A beta that is showing benefit in a clinical trial. However, the benefit was fairly modest. I think it improved by 6 to 8 months in cognitive function. Six to eight months is insignificant, but if you're declining like that and you're declining slightly less, is it perceptible?
I think in all of these, there are a couple of issues here. First of all, I think in this CNS area in particular, the animal models have not been very predictive of what is effective in the clinic. That's first of all. That's a real challenge. Mice are not men and behaviorally, some of these models look at mouse behaviors and how quickly they learn where a swim platform is or so on and so on. The methods are crude. I'm not sure the species translate. That's one issue.
Another issue is I don't believe we understand the biology of these things. At one point, somebody said the brain is the last frontier in medicine. I don't recall who said that, but I'm sure we can look that up. You can take out an organ before a person dies. You can look at lung function. You can look at sight or hearing, but it's not easy to look at the function of the brain as it relates to behavior, but also linking the chemistry in the brain, two of these behaviors. What do they do? They wait until a patient dies.
You've got a football player who had CTE and died at a young age. They take the brain out and examine the brain. They find the brain abnormal. I think that biology has a long way to go before we know enough. We're fortunate in Western society that there's enough funding to support crazy ideas. Those crazy ideas deserve funding, particularly in an area like diseases of the central nervous system.
However, the problem is that mice are not men. Let's say you want to study autism. How do you study autism in an animal? How do you study autism in a human? You're stuck mostly with behavioral, maybe some imaging technologies. I think there's a long way to go, particularly in the CNS area. There are other areas that are more mature.
There's a long way to go in our understanding before we're able to rationally develop a successful drug. The A beta hypothesis for Alzheimer's disease has been around for many years. There've been dozens of therapeutics that have targeted it. None of them have moved the needle very much, so why do we stick with it? We stick with it because that's one of the few things we know.
If I'm a not-so-young researcher working on and I'm interested in autism, what do you think that person should do to be a leader in the field? Should they build new models? What should they be focused on?
Let's start with education. You can't build a beautiful structure without a good foundation. First of all, they need to get the right training. As broad a training as they can, but they need to learn everything there is to know about neuroscience and the diseases they're interested in. To be a leader, you have to think out of the box. It's so easy to look at what's under the light, but the danger is that you're missing everything that's not under the light. That's how we get stuck in these dogmas and these ruts that everybody's doing the same thing, “A beta.”
I would encourage young scientists, investigators, medical doctors, or whatever to think out of the box and try to develop theories and hypotheses that, at some point, are testable. Maybe you need to extrapolate with something simpler to begin with, but never hesitate to think out of the box. You got to follow the data. You can't think out of the box and then never prove it and simply go forward with the data.
The scientific process is hypothesis and proof. To begin with, if you only think about what's known and follow the dogma, you're rarely going to come up with anything totally new. At least at the scientific level and the innovation level, that's what I say. There are lots of other things from a management standpoint, operationally and otherwise, that impact leadership but from the scientific level, that's what I think young people need to do is to think out of the box.
What you're saying is dare to go beyond incrementalism. It’s very easy to think, “I think it’s going to get me a paper,” but the reality is to think out of the box because you're going to meet resistance. Your supervisor, if you're a post-doc or a student, may not like what you're suggesting.
It's a balance because early on, if you're in an academic career, you certainly need to publish papers. However, I would say the two go hand-to-hand because the more you can think out of the box and prove your data, the more likely you are to be able to get a publication in a top-notch journal and get referenced, and so on.
I've published over 50 papers in my career. In the last few years, I haven't focused at all on that. There's something about writing a paper besides getting the information out there that proves your capabilities. It helps with your credibility. Writing a paper for the sake of writing a paper, I think even academia needs to find a way of quantifying the quality of papers. They do, to some degree, journal impact and things, but I think in many cases it's, “How many papers have you published?”
That's a whole other big topic for sure, but there are a whole lot of journals out there and you wonder. There are particular ones that are open publishing. There are some questions as to what quality these are. Is there any filter on or whatsoever?
When I look at a journal article, I think young investigators who are building their careers and credibility need to publish papers, but when I look at a paper, I don't look at what journal it's in. I look at the institution that it came from and the data. Peer review isn't necessarily the same in every journal, but you don't need to be in The New England Journal or Jammu or whatever. PNAS is an example. You don't need to have papers in those journals to have an impact.
Yes, those journals are ranked higher in impact score, but depending on your discipline, you can have just as much impact. Nowadays, with the search engines and PubMed and different ways with Google search, you can get the information out there more broadly without necessarily having to be in a top-notch journal. That's my opinion.
Therapies For Autism: In today’s age of search engines and PubMed, you can get your medical researches out there more broadly without necessarily being in a top-notch journal.
That's an interesting perspective about looking at the institution to make sure you're in the right environment to be doing your work because if you're in an institution that doesn't have the reputation, then perhaps it's less impactful to a degree.
It's a lot harder. The truth is that certain institutions seem to have, and it's not only a reputation but the people and investigators doing more cutting edge. I don't want to give the impression that you can't be at some smaller university or less well-known and do that, but you know what happens in the smaller universities in colleges. The teaching load is typically much higher and it's a lot harder to advance the scientific process from an innovation standpoint.
I want to go back to something you said because I thought it was a very interesting point. You mentioned that if you're starting off, you should learn everything you can about neuroscience. You've heard about the concept of flow. There's this idea put forth by this guy named Mihaly Csikszentmihalyi. He had this concept of flow, but he also wrote a book about creativity, which is very interesting because he went through a lot of classic famous people who were creative. One of the things he came out of as a principal there was that to be creative, you should learn everything about the field first, then you can be creative.
I think sometimes we miss that because people want to go quickly to get to the new stuff. However, it's only when you have stood on the shoulder of giants and understood what everything happened beforehand that you can truly be creative, which is a point in that book. I thought that resonated very well with what you said.
There are two aspects to that. The foundational knowledge, and again, I like to use building architecture as an example. If you don't have a strong foundation, I don't care how good your design is. It's not going to last very long. The other part of it is that I look at science as a language. If you don't have basic language skills, how do you write a book? How do you tell a story? How do you communicate?
Using the architecture analogy, you've got an architect who understands the structural elements, but he's able to layer on top of that the creativity. They can look at history. I'm sure you've been to Barcelona or if you haven't, definitely go. You’d see the Gaudi buildings and they're not just magnificent. They withstood the test of time. They're structurally sound.
Whether it was him or the structural architects he brought in, I don't know, but he certainly paid enough attention. These buildings are not falling down hundreds of years later. I think it's no different in science. You got to have that foundation, but the foundation is just a language. You can use the language to create this beautiful idea, as innovative an idea as you want.
The danger with history, at least in science, is that you let history limit your ideas. I think there's a danger of that. Many of us who have gotten PhDs many years ago, decades ago, now, technology advances so quickly. Now, you can probably do in a month what took me four years to do in my PhD. What's the story there? The story is if you have that foundation, I think you can be creative and the foundation does change over time.
I would say, like neuroscience, you got to have that foundation. You got to know what history is but don't let history limit you. I'm sure somebody someday will come up with a better political system than capitalism and democracy, but right now, that's the system we work within and you got to work with that as the foundation and work from there.
If your scientific ideas have the right foundation, you can be creative in developing it. This makes it flexible and able to change over time. Do not let history limit what you can do.
I think that's a nice parallel there. What's the most fulfilling project or outcome you've recently experienced?
If you are willing to allow me the advantage of time, I prefer to give you an example that is a little bit dated but is no less relevant. I started my career after my PhD and post-doc at Bristol Myers. I spent seven years and cut my teeth there. I started on the East Coast, which was a big corporate blue environment. There was lots of funding to do research, but the innovation part wasn't promoted internally as much as the competency.
Gene Dreams
Bristol Myers would bring in drugs from elsewhere and it was our job to evaluate them and then test them, but the drugs were usually developed elsewhere. At some point in the time that I worked for Bristol, they decided to move our immunology group out to a site in Seattle. The Seattle site was a biotech company called ANCA Gene and Genetic Systems. If you ever get the chance to read the book Gene Dreams, now it's dated, but there's an actual book out there that talks about the acquisition by Bristol Myers of ANCA Gene and Genetic Systems.
That site was 300 people. These were top-notch scientists. The site was publishing hundreds of papers a year. They were real innovators. They were people who were thinking out of the box. The reason they transferred our group there was they wanted the East Coast culture to oversee the innovators. Now, you can imagine that it was quite an interesting adventure, but there were some good things that came out of there.
I had started a collaboration with that group prior, but when I first joined, there was some early discovery work in the immunology area. There was an idea that two receptors signaled each other and told the cell whether to consider the response self or foreign. This, at the time, was only a theory, but these guys had developed a protein that could block that response. There's a scientific term called energy. Energy is when you can take an immune response to a specific protein and you can block it. It’s only that protein, no other protein.
It's a very selective way of blocking and you can imagine how this might have relevance to organ transplantation or autoimmune diseases. Your organs are rejected by a specific protein or an autoimmune disease where there's a certain autoimmune antigen that your body is responding to no longer itself. I came out there as part of the group and we were very much oriented toward translating the discovery results of the Seattle group into two products that could be developed.
I got involved with this molecule, which at the time was called CTLA4Ig. I published a paper in '92 in Science as the senior author on the first proof of concept of this CTLA4Ig blocking this co-stimulatory pathway and causing antigen-specific tolerance or energy. That drug later went on to become the drug ORENCIA. ORENCIA was originally approved for juvenile arthritis. Now, it's been approved for all arthritis and has been a very successful drug.
However, I can tell you that some of the earliest studies put this into animals and saw the impact of the drug. We used to transplant skin from one mouse to another. This was from a white mouse to a black mouse. If you transplant skin, particularly in a mouse, that's one of the hardest things to do. We'd create a wound. We'd take out the black skin and in a small region, we transplant the white skin. If you don't treat it with anything within three days, that white skin will totally crossover disappear and the brown skin grows back.
Using this drug, we were showing that you can maintain survival in grafts of white skin. When you stop the drug, it still survived. We created this tolerance. We talk about fulfillment. This was very exciting. Besides the paper we published, this was the basis for moving the drug into humans and the clinic. It took a long time to ultimately become approved by the FDA and elsewhere in the world, but to see something like that, some new idea with a therapeutic targeting of that idea, proved that this concept worked.
By the way, that pathway later turned out to be the major pathway for immuno-oncology, for treating cancers by activating the immune system. We never even thought about that at the time. Here's an example of looking under the light. The thinking was this is a natural tolerance second signal system. If you block it, you can initiate elicit antigen-specific tolerance, but if you activate it, which we didn't think about at that time. I don't think we had the reagents to activate it. You can turn an immune cell against the cancer cell. I wish I was smart enough to think about it at the time.
You would've moved the immune-oncology filled up by 10, 15 years.
However, only in terms of fulfillment, and it depends. I'm driven by translating science into a therapeutic. It doesn't have to be that. I think there are lots of other fulfillments in understanding basic knowledge and improving new basic ideas, but the idea of being able to translate the science into something practical to me is what I get my jollies on.
Was there something you had to do to convince them to make that step to translation? I think that's an important topic, and I've seen this perhaps as a growing trend as well to focus more on the translation from the basic science. I've had a number of projects where we're working to convince the basic scientists that you should be involved in this step. I'd be interested to hear if you encountered resistance to that idea. Did you have to give them some different directions on how to do that? How did that go?
You're right. I think less so now, but certainly, back then, this was in the early '90s, and there was tremendous resistance to translation. I don't want to say translation. Hardcore basic scientists are taught to prove their theories, but we know how much money goes into basic science. They're important questions. They're seeking knowledge, but not necessarily from a pragmatic standpoint. Yes, there was a tremendous amount of distrust and resistance when the East Coast group first came out to the Seattle group. “Who are these guys? They're spies from the East Coast.”
There were a few people talking about leadership. There were a few people in the Seattle group that saw the value of translating their basic discoveries into practical discoveries that could lead to therapeutics, but it was not the norm. I think still now, it's the way our academic system is set up. Yes, there's a lot of talk about translation, but I don't think many people do it. I'm not sure how much the NIH and the government support it in our country. I think getting out of that rut is very important as building that trust. Once we started showing positive results, they bought into it, which was appreciated.
Therapies For Autism: There is a lot of talk about translating basic discoveries into practical discoveries that lead to therapeutics. But in reality, not many people actually do it.
That was my next question how did they react? Did they walk away completely disappointed because it went the translation or probably not? They were probably even more enthused.
The leaders were very enthused. They're the ones who controlled more of the resources, so that worked very well. Some of the early basic scientists did not. They wanted the glory and they thought this took away their glory.
That's interesting because I've often thought it's only a matter of the frame that you're doing your science in because, for example, if you have a test compound and you put it in, that's a great perturbation for basic science and that's also meeting your translational goals as well. Why those two can't be complementary? Your focus is a bit shifted, but the basic science is probably as good or maybe even opening up even more avenues. As you said, maybe they could also use it to turn on the immune system to fight cancer. That would've been a fantastic basic science to finding the mechanism behind that. I'm sure there's some great basic science there.
The reason, or at least my interpretation, is some people are technologists and some people are more holistic than that. I think the Seattle site was originally a technology site. Early days of recombinant DNA, identifying new proteins on immune cells and trying to understand what those proteins did, but the technology was all about the expression of recombinant proteins. That was the core technology competency.
It was the few leaders that recognized that unless we can turn these discovery molecules into therapeutic molecules, then how can we justify being funded by a pharmaceutical company? Those were the leaders. By the way, those people went on to very high-level jobs in other large pharmaceutical companies or biotech companies, but that was not the rule. Even now, when people talk about translation, they talk about it. They say you need more of a pragmatic approach in getting NIH grants, but I think in reality, most of the NIH grants support the discovery process, not the advancement process.
It's very interesting there because what you're talking about is that people who didn't take a little more of a commercial perspective accelerated that innovation, which in the end, was hugely impactful. Sometimes people say, “That's a commercial perspective,” but a commercial perspective also has its rationale in the whole discovery and innovation process. By taking that commercial mindset, they accelerated the process or enabled the process to be accelerated.
Without those translational studies, the drug would never have moved forward, but there's mistrust. Those are the people who couldn't succeed at cutting-edge basic science. I run biotech companies that are developing drugs and in many cases, we're licensing what we think is a potential drug. It's early, but some initial translation has been done. We're doing it. There's no competition between the basic scientists and the translational scientists. If I had to structure a large pharma company and integrate both these groups, I would have two parallel groups and have incentives for the two groups to interact.
It's true that translational scientists are not going to be the best basic scientists and the best basic scientists are probably not going to be the best translational scientists. However, if you put these groups side by side and incentivize them in terms of candidates moving forward and proof of concept, I think that you will get people to rapidly come up with new ideas, produce a candidate, and determine whether that candidate can work or not. That's the first step. That's where the innovation happens. After that, it's mostly development.
Therapies For Autism: If you put basic and the translational scientists side by side and incentivize them, they will get people to rapidly come up with new ideas, produce a candidate, and determine whether that candidate can work or not.
It's a process and it's predictable. It's routine.
Toxicology is phase one and PK, and so on.
I think there's one other level now that, in recent years, you can add to that, which is even the clinician-scientists because getting the samples and being able to do the molecular biology, the omics, and all this can inform that whole translation process as well. You're then bringing those next to each other because the models have advanced to the point where instead of using a mouse, you can use human cells obtained from a patient. That's where it gets organoids and so on and so forth. That's where it gets even more exciting in this way of this combined effort.
I think you're absolutely right and there's been a lot more focus on that. There's certainly been a lot more work on that. The challenge in the CNS is you don't have access to the tissues, not at least in a live person. In other areas, like the immune cells or even cancers, it's much easier to access the tissues, but I think there are still large technological gaps. This is where people talk about machine learning and artificial intelligence. The problem is that you take a tissue sample, you take it from a healthy person and you take it from a deceased person. You generate a lot of data. How do you interpret that data?
If you look at the universe, if you look up at the sky at night, what sticks out? It’s the brightest stars and constellations, but in terms of context, you don't know how to interpret that. I think there's still a long way to go in terms of omics and information is not knowledge. Information data is what it is. There are people working on that. There's a lot of money going into that and effort. Certainly, having the physicians with access to the patients and studying this is helpful, but I think we're still a long way in most diseases from using that in a way that's ideal.
I'm part of an advisor with a startup that's working on that topic.
We talked about that previously and I'd love to get more and more involved in that.
I will bring the connection and it's called TopMD, for people who want to know. I don't want to make it clear that's an endorsement, but I have a relationship there, so people know that. I think it's exactly what you're talking about.
That’s how we met. That's of interest to me, for sure.
The next question I want to ask is shifting gears a bit, but what was the lowest point of your career and how did you get through it?
When I first joined a venture-backed company in 2002 as a second CEO, this was at the time the human genome was fully sequenced. We were trying to develop a radial disc to screen tens of thousands of targets against hundreds of thousands of compounds. That was the basis of the company. Originally, they were developing it as a tool company. They wanted to sell a device that could do that. I think they realized at the time that it was probably a long haul and a very expensive goal.
We changed the company vision to using the tool to serve others in that discovery process. I came in and I changed the company from an instrument company to a discovery company, but there were a lot of things I didn't know. I came from an environment where if you had the idea, the money was there to do the work as long as it fits within the mission of the institution. Money was no object. The investors put in money when I came in, but it wasn't a lot.
I assumed that they were prepared to put more money in when this ran out. As I did in large pharma, I didn't cut off the instrument development because it was an important part of what value the company was, but they were developing this instrument as a marketable instrument. I won't name the name of the company, but we worked with a company that specialized in building marketable instruments. They developed dental chairs and things like that.
The burn for that was very expensive. It was an engineering team. I didn't cut that off because that was the innovation engine of the company. However, it turned out the prototype they built up to that point proved the concept of being able to do screening on these radial discs, but not in a way that can be used to service pharma companies and offer them a service to do this. It only proved that you could do it.
I ended up not only joining the company but having to shut it. I recruited all these top-notch people, great people on the BD and the scientific side. I restructured it. We built the labs to do what we needed, like chemistry and biology. The money ran out after a year. I couldn't raise additional money for a number of reasons that I had no idea of when I joined it. I had to shut this company down. I had to lay off everybody.
I had to make it down the board how much we would need and how long it would take to get to the next step. I didn't realize that it was only invested in by one VC firm, and they had pretty much reached the cap of what they could put in, so they couldn't put in any more money. It was like a real rollercoaster ride and winding down a company is not simply shutting the doors. There are all sorts of legal things you need to do and assets that need to be sold and so on.
It was a great learning experience but not a great professional career experience. Not only that, I won't mention any names here. As you might expect, I was an executive-level person in pharma. I joined with a severance package and the whole bit. They never gave me my severance. When we wound down, we didn't even have a severance. I had to start from scratch. I went ahead and started another company that we went public after that in the RNAi space. I can tell you at the time, and this was 2002, 2003, it was a real low point.
How did you get through it?
I have a philosophy with all of my companies and all of my efforts, persistence, perseverance, and passion. I call them the three Ps. In my last company, Corbus, on the wall, we have this written because we each got to write a little blurb and sign it. That was part of our culture. Persistence, perseverance, and passion. I love what I do, even if it doesn't always work. You absolutely have to be persistent if you're going to raise money. You got to kiss a lot of frogs to find a prince.
You have to be persistent if you want to raise money. You need to kiss a lot of frogs to find a prince.
I have three kids and I tell them all the same thing. Go after your passion. If it's your passion, it's not going to feel like work. I encourage that. In life, there's pragmatics also. We're all in different circumstances. We all have different family situations, so not everybody can necessarily pursue all those things. I've been fortunate to be able to pursue all those things. To me, if your compass is based on your internal drive and not validation from others, you do need that validation now and then, but I think you can overcome these things. I don't think it's anything different than life. I think the same applies to everything in life.
That's a very good way to put it. The question I want to ask you is, what do you do when nobody else is looking that improves your skills?
First of all, I'd love to say reading, but I don't get to read enough. There was a time in my career when I spent a lot of time in terms of what you might call soft skills. Self-help books and the Harvard Business Review gives a lot of anecdotal examples of various issues that other companies have dealt with. I think age also is like a fine wine. The age does mellow you. I was a very hard manager early on in my career. I'm not happy to admit it, but some employees cried because I put a lot of pressure on them.
I don't do that anymore. Why? It’s because I've learned it's not productive for anybody. I would say reading is the one thing I'd like to do more to improve myself. By reading, it doesn't necessarily have to be science. It could be other things. It's not just fiction. You could read fiction. That's fun. When I go on vacation, I usually try to read a book or two on fiction, but what I'm talking about is continuing to expand one's knowledge base, both in terms of hard as well as soft.
I think that's the theme. We've now done probably 15 or 20 of these interviews, but the theme that's emerging is if you want to be a leader in life sciences and healthcare, you need to do more than just read science. You need to do that external stuff. That transferrable skill is what some people call it as well, besides soft skills. That's not necessarily intuitively obvious when you're in the midst of your development. That's a good point.
Again, it goes back to that foundation. You need enough of the foundation, but leadership isn't simply about what you know. It's about whether you can recruit the talent and motivate them and incentivize them to even be better than you. That's certainly something that, at least in my startup companies, I've always sought out. My successes are not simply my success. They are from the success and talent of other people.
If there's anything that I have learned, it's to surround yourself with smart people that know more than you. Nowadays, they can be younger people. It doesn't matter the age, but I do think that as you get older, you are a little less creative. The foundation has changed a little. The younger people have learned newer things. If you rely on older people, and I hate to use age, but more experienced people, you are not going to get the same level of innovation.
Therapies For Autism: Surround yourself with smart and young people that know more than you. If you only rely on older but more experienced people, you cannot get the same level of innovation.
Do you follow a strategic planning process in your companies and startups? Do you develop a strategy with those people around you? How do you do that?
Constantly. You may have heard the term pivot, but you can't do a startup or an early-stage company without pivoting. Pivoting means being realistic and looking at the strategy and making sure the strategy still fits with the data you have and what you're targeting. I've learned to be very open about that. We have team meetings. There are different team meetings for different projects, but we have them every other week.
In those meetings, I'm always updating people or re-discussing the strategy because I want people to be self-driven. I don't want to micromanage and tell them what they need to do. I want them to see the horizon and then build what their expertise allows them to build to get to that horizon. If you don't share a strategy, getting input from others on the strategy helps gain buy-in on that strategy.
People who feel involved and that their input is valued are much more motivated to contribute than those who are dictated to. I'm not saying everybody's that way. Some people would rather be dictated to. They may not want to take responsibility, but that doesn't mean you can't have a discussion on this strategy and open it up. This goes back to multinational.
The more you get input from other people on the strategy, the more likely you are to have the best strategy going forward. If it only comes from the top down, again, it's that light. You're only focused on what you're interested in and what you think is important. Unfortunately, I have to be honest. I don't always get the feedback that I would like to get. Certain people are leaders and other people are not.
That’s an interesting point that actually, when given that opportunity to give feedback, is a form of leadership, even though they're not the leader of the company. When you say, “What do you think?” Saying what they think is about being a leader as opposed to saying what they think you want to hear.
In business, that's true too. You have to be willing to ask the yes-no question and potentially get the no answer to lead people. If you are afraid of the no answer, then you are pushing people up the hill. It's a lot easier to have people climb the hill themselves than pushing them up the hill. Even if those people don't want to give their input or are shy or it's not in their nature, you at least give them the opportunity by opening it up to them. If they don't want it, then maybe they're perfectly content with somebody else calling the shots, but to not do it is basically to dictate. As I said, I like to hire smart people. Smart people are not typically the ones that want to be dictated to.
It is a lot easier to have people climb the hill themselves than pushing them up the hill.
One more question that I'll ask you is one that I think everybody that I talked to deals with. How do you manage all your competing priorities?
Not very well. I always have in my mind, if not on paper, what the highest value-generating priority is. Right now, I'm out fundraising. I got $20 million committed to a $35 million round. One of the projects is funded by that $20 million, but we need the other $15 million to fund the other project. There's nothing more important to me than raising that money because without that money, I can't do what I believe is value-generating for the company, or at least not completely.
I have either, again, in my head or on paper, you can make it a to-do list, but I almost always prioritize the highest value. It's like going back to college. You had tests coming up. Maybe it was finals. Let's say during the academic year, you had tests coming up. Maybe they were separated by a week or two days, but you knew when they were coming up and you knew what your priority was.
This is an area that younger people have a particularly hard time with when they transition to work, where nobody says this is what you have to do. I always made it a point. I knew what the next test was. I'd start studying 3 or 4 days before. Typically, if I had two, I'd study half this and half that. It's the same thing. I want to focus and make sure that my number one priority is taken care of and not shortchanged.
I juggle the rest of them based on how important they are. It's hard because, particularly in a startup, fundraising, strategy, and operations are always competing with each other. What I find gets shortchanged for me is the operations. I love to be involved in the operations and we're still fairly young. At some point, I'll hire somebody to do that role. That's the way I do it. I'm sure there are more efficient ways to do it.
I also think it's good to point out that this is a problem for everybody. Juggling priorities is hard and not to be frustrated, but to keep moving and trying to do it because everybody struggles that way.
We didn't even talk about personal priorities, family, and stuff. They probably get shortchanged and that's a danger too. If you talk to people on their dying bed, they don't talk about their careers. They talk about they wish they had more time with their family. That's irony, and that's, again, something that I think Europeans and other countries are better at than Americans.
You also have to prioritize walking through Rome and drinking wine.
That's why when we did it, and again, this was a Eurocentric company. It’s multinational but Eurocentric. That culture was already there in the company. In the US, it tends to be less so. The leadership is able to create the culture of the company. When we went public with my last company, Corpus Pharmaceuticals, we rented a bus and we took everybody down to New York to Wall Street to ring the bell for the NASDAQ. That was a milestone for everybody. We took lots of pictures. I guarantee everybody involved in that has a fun memory of that.
You do have to create time for some of the things. I have seen managers who equate time spent in the lab or whatever with productivity. The most productive are people I've seen that leave at 5:00 and go to their family, but they've been very efficient with their time. It's important to balance these things. It’s hard to do.
I've learned a lot and been inspired a lot by you. Is there anything else you wanted to say or comment or bring out?
No, I hope that your audience gets some value out of this. I've been doing it for a long time. Without tooting my own horn, I think I've been fairly successful but there are ups and downs. I'm approaching the end of my career, but to have a career that you could look back on and feel good about and not feel like you slaved, “I worked very hard, but it's been fun. It's been enjoyable.”
There is a time for publications, but publications are not everything. If you find that that's everything or you're being evaluated only on that, I would question the environment that you're in. I don't think that's the whole thing. There are times where it's very important. Don't get me wrong. That's the only message. I would say follow your passion and be perseverant and persistent. I think if you do those things, you'll succeed at whatever you do.
Therapies For Autism: Publications are not everything. If you are being evaluated only based on that, start questioning the environment you're in.
That's a very good way to end this. Once again, thank you very much for coming on.
Thank you, Scott, for the opportunity. I'll look forward to seeing it released.
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About Dr. Mark Tepper
Dr. Tepper has over 30 years of experience in the biotechnology and pharmaceutical industry. He has led drug discovery & drug development programs that span a wide range of therapeutic areas including Oncology, Immunology, Rheumatology, Endocrinology, Metabolic Diseases, CNS, Inflammation and Pain. Following a 15-year career in large Pharma R&D, in 2002 Dr Tepper left large Pharma to become a serial entrepreneur where he founded multiple successful biotech companies. In leading these companies, he served on the executive management team, helping to execute on the business & commercialization plan. In the last 15 years, Dr. Tepper has raised over $200M in capital for his ventures. He has taken two of his companies’ public (Corbus Pharmaceuticals and RXi Pharmaceuticals) and sold another company (Primatope sold to Kiniksa) in a trade sale.
Dr. Tepper earned a Ph.D. in Biochemistry & Biophysics from Columbia University, College of Physicians and Surgeons, New York, and a B.A in Chemistry with Highest Honors from Clark University, Worcester, Mass. He did his postdoctoral fellowship at University of Massachusetts Medical School, Worcester in the laboratory of Michael P. Czech. He has over 50 scientific publications and is the co-inventor of multiple drug related patents.
