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David Baram: Founder and CEO of EmendoBio · BioBoss

• 0:00
  John Simboli: Today I'm speaking with David Baram, founder and CEO of EmendoBio, headquartered in New York. Welcome to BioBoss.
• 0:07
  John Simboli: David.
• 0:08
  David Baram: Thank you, John.
• 0:08
  David Baram: It's a pleasure to be here; looking forward for a delightful discussion.
• 0:14
  John Simboli: What led to your role as founder and CEO of EmendoBio?
• 0:17
  Unknown: What led me to be the CEO of EmendoBio, eventually founding the company together with, actually, a group of friends. Most of them graduating from my class, I gathered a couple of them together around the idea of creating the next generation CRISPR gene editing companies. We have all found CRISPR gene editing fascinating.
• 0:39
  Unknown: It was somewhere we wanted to be. We all gathered our own data, and I took the role of the CEO.
• 0:47
  John Simboli: I feel like I've known you for a couple of years.
• 0:49
  John Simboli: And I think a word I might describe you with, if someone said, what kind of work is David doing? I might say he's a serial entrepreneur. Would that be what you describe for yourself?
• 1:00
  Unknown: I'm definitely an entrepreneur since I was a child. I found my, entrapreneurial way in several applications and I have founded several companies within the medical space, mainly, but not only. So yes, you might say that I'm a serial entrepreneur, but I think I'm just an enterpreneur.
• 1:23
  Unknown: It doesn't really matter if you make one company or several, eventually. I enjoy founding, establishing new businesses that potentially would not have existed if I wouldn't have done so.
• 1:36
  John Simboli: And making the choice to found this particular one, can you recall the sequence that led up, with the probably hundreds of ideas you were considering and contemplating?
• 1:47
  John Simboli: What was drawing you to this particular one?
• 1:49
  Unknown: Actually, you know, I'm a scientist by training. And before CRISPR, or let's say before, I had founded Emendo, let's say if you took me 10 years before that. And you would have told me, you know, in 10 years, you will establish a company that manipulates people's genomes in order to cure them, I would say "Come on." Now 10 years. I saw it coming but not 10 years, 2030, I don't know. A couple of years after, you know, CRISPR gene editing or the CRISPR technology was found to be effective in mammalian cells by Jennifer Doudna and Emmanuelle Charpentier. There were others back then, but they got the Nobel Prize for this amazing invention. And then, immediately after, like the three first CRISPR, gene editing companies were founded—we're talking about 2014. Now I say wow, that means that it's really happening. And then I say, OK, if this is happening, I want to join that race. But then came another question, just a moment, that was invented, already, not by me, three companies were founded already and there are going to develop therapies based on that.
• 3:17
  Unknown: Where do we come to this industry? What will we bring, that will make a significant difference? And that's how we started. We said, OK, there's this amazing technology, but it's just in its very first stages. And if there's something that I knew back, I knew biology very well. And if there's something that I know about biology, that it's unexpected.
• 3:52
  Unknown: For instance, you take CRISPR, you think it works like magic, right? You have this amazing tool, you send it to edit whatever you want along the genome, just replace this RNA cassette and it works like magic. Well, for those who are experienced with biology, you know that, almost always, it does not. We were sure that there's a lot to be done there.
• 4:14
  Unknown: And that's how we started, we said, OK, we believe in cures, I think these are fascinating, transformative times in healthcare, generally, the fact that we're actually talking about developing cures. And then we wanted to bring it to more and more people. And we said, OK, how do we help in closing the gap? At the beginning, as I said, we're manipulating people's genomes. Wow. But the promise is so huge that you want, eventually, to be able to get this to as many humans as possible, and to cure as many people as possible. So what is the gap and what is our, Emendo's, role in closing this gap between a novel new transformative technology, making it a reality for as many patients around the world?
• 5:13
  John Simboli: I was thinking back. And at that time, it seemed like the challenge was how can we help to explain it's not as scary as it sounds?
• 5:21
  Unknown: There is a reason why our DNA and our genome is packed within a very well protected environment within the nucleus, within the cell. There's a reason for that. It needs to be protected. And now we're saying OK, we have this technology, we can get in, we can change it, but it was protected for a reason. And I have found that, while I'm not scared easily, but
• 5:46
  John Simboli: Was part of the way that you went about solving I'll use the word scared. And this led me, and us, together with my partners to choose the first challenge for Emendo. As I said, before, we said this amazing technology that can potentially cure people, we would want to cure as many people, as many diseases as possible. But we thought that the only way to get there is to deal with safety concerns and safety issues first. Safety will lead will lead the way. There's a reason why when you develop a drug, first, you make sure it's safe, then you make sure it's efficacious. Righrt? There's a reason for that. And we thought that the first thing that we would want to do in Emendo, is to make every effort, use any technology, scientific tool, that is out there in order to try and eliminate the off-target effect. And the reason for that, by the way, just one last thing is past experience. Gene therapy. 90s, late 90s, we had some unfortunate cases of patients . . . Gene therapy was back then the promise of gene editing of a decade ago, was the same. And there were some unfortunate cases, and it held this space for quite a while.
• 7:12
  John Simboli: And we said that we will focus first on that. We'll make it as safe as possible. You know, at the beginning, our investors back then we said, OK, we had on our deck, on our corporate deck, we said, zero off-target. That's what it was, we said zero off-target and they said, are you sure you want to say that?
• 7:36
  John Simboli: We didn't know back then if we'll be able to get there. We did know that it is the obligation of the entire industry to aspire to get to zero off-target effect. Whether we'll get there or not, we didn't know. Fortunately, I can say that later on, we were able to get there. When I say zero, I say non-detectable off-target.
• 7:58
  John Simboli: We actually presented the FDA with data that shows non-detectable off target altogether, this, it's ongoing, I understand, is part of the way you're going about solving this to look very particularly at a given disease and to try to find out how the technology might be applied.
• 8:24
  Unknown: That's a big part of it. But it's not always necessary. So the approach that we took from the very beginning, we chose an approach that says there is no one solution fits all. So I think that when most of our competition tried to work on having a single editor, a single nuclide, and to engineer it as much as possible in order for it to be as broad as possible. That means to target as many genes as possible and target as many locations along the genome with no off-target and for it to be highly active.
• 9:03
  Unknown: We thought, back then, and we still hold the same approach, there is no one solution fits all. There's no one nuclide, the same way there's no one antibody or many other, I can give many other examples. So we generated a panel of tools that allow us to target as many diseases or genes as possible. And then on top of that, we engineer them in a very effective and fast manner for a specific target site or target gene. And I think that's the unique approach of Emendo.
• 9:49
  John Simboli: Even investors who may not be specialists don't always appreciate the role that the CEO has, as opposed to the role of the scientist-CEO. You are a scientist, a CEO, a founder. So I guess part of the question is, how do you spend your day as a CEO, a founder, a scientist?
• 10:07
  Unknown: It's a good question, because I'm a scientist by training. I'm an enterpreneur.
• 10:12
  Unknown: And I think that behind all of that, if I think about my passion, I think it eventually starts with the science part. I think that I had intrapreneurial skills, and curiosity as a child. I think that when you have the skills to lead, you can become the CEO of anything. But I don't want to make any other company in any other space. And I don't want to be the CEO of anything else but, in this case, Emendo. But a science based company. For me, personally, the content is a crucial part in this. But I think that I wouldn't have chosen to do anything else, I really enjoy the scientific part of it. Now, unfortunately, along the years, as your company grows, you allocate more and more time to the business part on account of the scientific part. But, being me, I am always very involved with everything that happens in the company in terms of R&D. I don't really let go. I can't manage daily details, but I'm very, very involved. And I intend to continue doing that.
• 11:48
  Unknown: Because eventually, that's where the value comes from. It comes from the science itself, it comes from what you know. This is a startup, it's based on R&D.
• 12:02
  Unknown: That's the heart of the company.
• 12:05
  John Simboli: If your curiosity about the science is probably, I guess, insatiable is probably a term for a scientist, how do you then balance that with the need to work in a team and to avoid the smartest guy in the room trap?
• 12:23
  Unknown: When I look at Emendo, I look at the people that work with me, the people who work with me, I think they're some of the smartest people that I know.
• 12:31
  Unknown: I do not try to avoid the smartest person in the room, I try to enjoy having the smartest person in the room. But I think that, for me personally, I would say that I don't think that I'm the best in anything. I want to have people working with me and working under me, that are better in what they do, than me.
• 12:59
  Unknown: The thing is, and I think that's the skill that I have. I know enough, and even more than enough, about many aspects of the business. For a long time, I could say that I have done almost any job that is being done in the company. I've managed R&D, I've guided all aspects of the company. I was also a scientist, I did my PhD, I worked on the bench, I did research. And I think it gives me a lot of tools to also manage the people around me and connecting the different different dots and elements. And I think that that's what you need to do as, as a CEO, eventually. So you have your science that is dependent on the business side. And you need to know, the operation to hold the entire thing and to enable the scientific work. You have the legal parts, you have a board to manage, but it's all connected.
• 14:26
  Unknown: So being in the middle, understanding enough, each and every one of these pieces and then combining them into a picture that makes sense and into a company that has a clear direction, that is something that I enjoy very much.
• 14:44
  John Simboli: How does one cope with the fact that there's probably a greater deal of uncertainty in this field, being leader of a biopharma CEO, then lots of different things you might be a leader of?
• 14:54
  Unknown: You learn to love uncertainty. You learn to enjoy uncertainty. Actually, I wouldn't be comfortable in another environment, in a more certain environment, because I find this specific question a very interesting one. I think that wherever there's uncertainty, there's a need for leadership. When things are certain, and things are clear, leadership is not as crucial or critical. These are exactly the times where you need leadership and you need leadership that is calm, that is not that troubled by the uncertainty that is able to say to everyone, well, sometimes we do not know but we have to do something and just start walking, taking that direction with confidence. And I think that I enjoy these parts vary, very much. Because the questions that we deal with are usually of a high level of complexity. Whenever you have a high level of complexity, the uncertainty is inherent. And I think that there's a reason that I went there. I'm very comfortable there and I even enjoy the challenge. It's more important to make a decision than to choose the right decision. To make a decision, not to avoid making a decision, to stand behind it. To always know that a decision has to be made and you have done everything that you can to get all the information that you need in order to make the right decision and then you have to make it. Sometimes you will be wrong. And understanding that there is no other way and taking the decision, is a must, because you have to move forward and you have to navigate. Even if you if you made the wrong decision, well in most cases you can fix it after. It becomes even more scary when you develop drugs and you're in the clinic and there are lives involved and then it becomes even even scarier. But all it should make you is aware and alert. But you will still have to make a decision. It's not that you have a choice. It's not that you can make a choice not to move on. You have to. So accepting that, knowing that, I think helps a lot in just making a decision. I get this time, I have to say this or that. OK, take one. And be aware, open your eyes along the way, look for signs to see. Even after you make a decision you, there are many times you can choose another path along the way and be directed to a better way if you see, let's say, warning signs. We always have to check ourselves, to check our decision. Never regret it; just fix it if you need to.
• 18:28
  John Simboli: Can you remember, we were talking about your your lifelong interest in, curiosity about science, can you remember when you were a kid, did you have that curiosity? Did you have this picture of, someday when I grow up, I'm going to be a . . .
• 18:41
  Unknown: I knew that I would want to fix things. I think there's if I go back then, I would have probably thought I would have chosen something like engineering or something like that. I have actually two examples this from my childhood.
• 19:04
  Unknown: I really liked disassembling things and then putting them together in a way that will make them better. So I would take each and every toy that I had, and I would do that. Most times I failed. One time I did with my father's very expensive camera and this didn't go well because I couldn't actually assembe it back, nor could he. I have one memory that I have from the childhood, actually when I was nine. I had this remote control, high-speed car that I crashed into the wall in a race and it broke and I knew that my parents wouldn't get me a new one for a couple of years, for sure. So I broke it into the smallest pieces. I went and bought parts and took other toys, and I built a whole new car. And this car ran for 10 years after. You know, don't give up when things break,, take it into pieces, reassemble that. And I think that if I go back then I would say, yeah, probably an engineer.
• 20:23
  Unknown: But now I'm, in some ways, engineering the human body. So the complexity of that is even .
• 20:39
  Unknown: . . I see today why I chose that and nothing else.
• 20:45
  John Simboli: David. what makes EmendoBio different from other biopharma companies?
• 20:50
  Unknown: My immediate answer would be the people. Emendo is a startup company, we're eight years old, very few people left the company until now. People could have switched, people could have left to go somewhere else. I've worked with the same management, some of them for eight years, some of them for seven years, we only added people. Very rarely do people leave Emendo, as a company. Now, I'm saying it as a differentiating factor because it's unusual within the industry. And there are a couple of things that are very, very positive about that. A company is a living organism, I think that we were able to create an environment within Emendo that will make people want to stay.
• 21:41
  Unknown: There are very talented people and as the CEO of the company, I don't fool myself, I know that they have many other opportunities. Being able to get such a great retention rate with people means that we keep all of our know-how. This is know-how and experience that the people developed along the years. We keep on enjoying that. If people don't leave the company, that means that they believe. These are the people that are generating the data, they're generating the science, they know the smallest little details of everything that happens in the company. And if they stay for such a long time, that means that they believe. They believe that they're a part of something that is going to do great things, and is going to work eventually.
• 22:45
  John Simboli: Can one know ahead of time that you're hiring people who are in it for the long run? Or is that just something that you find out?
• 22:52
  Unknown: We built the company that we want to work in. Humans are the same, it doesn't really matter if I'm the CEO or I take another role within the company.
• 23:04
  Unknown: We want the same thing from our working environment. We want it to challenge us, we want to do significant things. We want to be appreciated. We want to succeed. Just making an organization that give that to people, gives people what you want for yourself, and I believe that you'll be fine.
• 23:28
  John Simboli: David, how does the pipeline express your vision for the company?
• 23:31
  Unknown: If look at Emendo's pipeline, you will see that it's well differentiated. Our lead indication,, severe congenital neutropenia, is an autosomal-dominant disease. That means autosomal dominant or dominant negative. That means that we have it for every gene, we have two copies, right one we had from one parent, the other one we get from the other parent, and autosomal dominant diseases, you have one copy of the gene who is healthy produces a healthy protein eventually, and in many of the cases this protein is important. And then you have another allele which is mutated. And the mutation, in the case of dominant negative indications, causes a toxic effect. And a toxic effect is actually the cause of the disease. That's the case of ELANE or severe congenital neutropenia. Now, going back to the story that I said at the beginning of Emendo's initial and most important objective, we said that we want to get precision to be so high that we will eliminate the off-target effect. So we got our nucleases to be so precise, that now we're able not just to differentiate between the on-target side, which is actually the side that you want this genetic editing or genetic manipulation, and the off-target sites, which are different sites along the genome that you do not want to interfere with. The highest bar is to be able to differentiate between the two alleles, or two copies of the same genes that have very, very small differences between them.
• 25:29
  Unknown: Usually, these differences are of one single base. And that's the highest bar of specificity.
• 25:38
  Unknown: So we got our nucleases to be so specific, and we said, OK, so what can we do that others cannot and then immediately we went to OK, we will do allele-specific editing. That's why Emendo is the first company to file an IND on allele-specific editing. That's one example. Now, ELANE, or severe congenital neutropenia, is a rare disease, rare genetic disorder that we of course, would want to cure. But again, taking you to the beginning of our conversation, another thing that I said, that we wanted, our goal from the very beginning, was to make this specific tool available for as many patients as possible, eventually. So it makes sense to start with severe, rare, monogenic diseases like ELANE, but then you want to go and target additional diseases, more prevalent diseases. And I think the entire industry is going there. So for our next indication, if the first indication, by the way, I haven't said that, it's an autologous ex vivo approach.
• 26:58
  Unknown: That means that we practically take the cells out of the body, fix them outside and then we plant them back into the patient after we fix them or edit them.
• 27:09
  Unknown: For the next indication, we chose to go after hypercholesterolemia. With the first indication, I think that we are first in class. There is no gene editing solution that targets the same disease because you need to be able to do allele-specific editing in a broad manner. For the second indication, we're not a first in class, but we believe that we can be best in class. And I think we wouldn't choose an indication, at the moment, that we wouldn't be either first in class or best in class. Why do I think we're best in class? The second indication is hypercholesterolemia or starting with familial hypercholesterolemia. We looked at the existing solutions with statins that many people know and PCSK9 inhibitors. There are also gene editing companies like Verve that are developing knockout approaches for PCSK9.
• 28:18
  Unknown: But the thing is that there are around 7 million patients in the US and EU that are not at goal with their LDL C levels, although they're both on statins and PCSK9 inhibitor. So we said there's a need for something else here. And based on our platform that allows us to target any site along the genome, and it's highly specific, we were able to develop a novel editing approach, that actually up-regulates the expression of the LDL receptor, to a level that we believe will allow us to, potentially, develop a one-and-done treatment for hypercholesterolemia. So that's something that we're very excited about now, as opposed to developing your first indication orphan disease for 1000s of patients. Here, we're talking about millions of patients. And I have many more examples from our pipeline, how it is unique, differentiated. And again, if I go back to speaking with investors or partners, I tell them if you want to understand what Emendo's platform is capable of, look at our pipeline, look at not just the genes themselves, look at the editing strategies. They're all well differentiated.
• 29:57
  John Simboli: I know you've been at this for eight years and I know that work is continuing.
• 30:00
  John Simboli: But do you find yourself at this point, willing to say to yourself, you know, if this thing really works, and I think it will, it will have this effect on patients? Or is that something, you as a scientist, you just wait and see?
• 30:13
  Unknown: Yeah, that's a major, major driver for me, personally, I feel that I'm part of a vision, and we take part in changing healthcare as we know it. And I think that healthcare is actually going to change and be something different than what we were used to until now. For, I don't know, maybe 100 years, the whole pharma industry evolved around, in many cases, by the way, around treating symptoms. We're actually curing people, or potentially curing people, or aspiring to cure people. I think for the first time, the industry is evolving into being able to offer patients to become healthy. Now think about that mentally, just think about if someone is sick, and you're giving him the option, not just to ease his symptoms, to become a healthy person. That's curing, that's the meaning of curing. It's not about just, you know, the physical elements here. It's about the mental elements here.
• 31:32
  Unknown: And what does it mean to have a patient that is now healthy?
• 31:37
  Unknown: What does it mean for society?
• 31:37
  Unknown: What does this mean for healthcare? And I find this to be fascinating times in healthcare, and I think that biotech has a huge part in it.
• 31:52
  Unknown: And I believe that gene editing, specifically, will have a very significant part, together with other technologies, of course.
• 32:03
  Unknown: It's not that I think Emendo or the gene editing companies are doing that alone. But I think we feel that. We feel that we're part of something big.
• 32:17
  John Simboli: David, thanks for speaking with me today.
• 32:19
  Unknown: Thank you, John. It was a pleasure.