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When I originally spoke with doctor Neil Kumar, the founder and CEO of Bridge Biopharma, he was very direct. Genetic diseases are solvable. Today, we'll hear from doctor Kumar about what he means and about the innovative corporate structure of Bridge BioPharma itself designed for innovation and success. Doctor Kumar, welcome back to the program.
Dr. Neil Kumar:Thank you so much for having me again. I really appreciate the time.
Dr. Moira Gunn:Now you have said to me when we were talking earlier, and it really hit me, I have to say, genetic diseases are solvable. What do you mean by genetic diseases, and why do you say they're solvable?
Dr. Neil Kumar:Yeah. So when I talk about genetic disease, what I'm talking about are mostly inherited diseases, what we call Mendelian diseases in our business. And these are diseases that you can trace back to the common source. So it'd be a point mutation or a single gene that effectively is driving all of the pathology that you see for patients. And the reason that that's important I mean, if you sort of think about it, I'm a engineer by training, and all of the major advances that have occurred in any engineering discipline come when you can measure things.
Dr. Neil Kumar:When you can you know, chemical engineering, for instance, it's like we used to put stuff in a reactor and then try to get plastic out of it. And then we started to be able to measure temperature and pressure and all sorts of things. And then reliably, we could understand what the system was doing and therefore solve problems. For these types of diseases, we can measure everything that goes on from the beginning, the insult, which is the mutation, to what's happening inside of a cell, and you're made up of trillions of cells, to then what the cells are doing at a tissue level, because you've got all sorts of tissues, could be the heart, could be the kidney, etcetera, to then ultimately what's happening for the patient. And because we can describe the condition or the disease with that level of clarity, that is primarily what makes it solvable.
Dr. Neil Kumar:So we know what's driving and we know how we might be able to, what we call it, bridge bio, target the disease at its source. So effectively take the causal driver and reverse it if it got too much of it or, you know, obviously to turn it up if you got too little of it. So the the the the the simplicity with which we can describe these conditions is effectively showing you that they are solvable, unlike a whole variety of other conditions where they may be some genetics, some environment, some okay. I you know, there was some acute injury, you know, physical injury of some sorts. These are much simpler diseases.
Dr. Moira Gunn:So this is the area in which Bridge Biopharma is focusing, and I shouldn't have said that just coming off of much simpler diseases because there are no simple diseases. And, looks like a typical biotech in the sense that you've, got 2 drugs already developed and approved. You've got 20 more drug candidates in the pipeline, but that's sort of where typical biotech company stops for me. In fact, BridgeBio is a number of companies.
Dr. Neil Kumar:That's right. And, you know, what we were trying to do like any biotech or startup, we were trying to solve a problem that was immediately in front of us that we couldn't solve any other normal way, I suppose. So, think about when we started about 8 and a half years ago, many of us were in a venture capital firm. We were working in the same area of genetic disease. And every time we had an idea, we would start 1 company at a time, and that is a very long process.
Dr. Neil Kumar:You go to the venture capitalists. You get approval. You build the company. You find space. You hire in chemist, etcetera, etcetera.
Dr. Neil Kumar:And so that's a couple years, and then you have another idea, and you take another couple years to do it. And another idea, you take another couple years to do it. And each idea needs to be big enough that it can kinda stand on its own and potentially go public or get bought by pharma, etcetera. Whereas, when we were looking at the playing field at that time and when I say playing field, I mean all of the wonderful work that was being done in academia that provided the substrate for new novel drug discovery and creation, we said, man, we we can't wait to just start each company every time. It's gonna take us decades to do this.
Dr. Neil Kumar:So can we start 1 company that goes after all of this opportunity at the same time? And our our thought at the time, and I think we were we've been wrong on a lot of stuff, but we were right on this, was that ever cheaper genome and exome sequencing coupled with all of these amazing databases like the UK Biobank and Finjan and what the US is doing in terms of sequencing all these genomes and putting them together with hospital systems. All of that information was gonna create even more opportunity for us and that we needed to create 1 thing that we could push it all forward. Okay. So now how do you do that?
Dr. Neil Kumar:You have to do a couple of things. 1st is you have to have some centralized infrastructure, so you've got all these different ideas that you're pushing forward at the same time. But the second thing you need to do is you need to preserve focus at the level of each biology because biotech wins in my mind because you have super specialists that just wanna solve this condition. So I can be working on ATTR cardiomyopathy. I'm an expert there.
Dr. Neil Kumar:I could be working on pantothenic kinase deficiency. A separate set of people are expert there and on and on and on down the line for the disease we work on. So the way we solved focus at the level of each biology was we housed each idea in a separate company or affiliate. And then the way we solved for diversification or being able to take on all of these ideas at the same time was that we provided a centralized infrastructure that took care of the things that were common across all of the ideas. Could be manufacturing, could be finance, could be etcetera, etcetera.
Dr. Neil Kumar:So that's kinda how we set it up, and that that's really what gave rise to the funky to the funky corporate structure.
Dr. Moira Gunn:I don't know if it's funky.
Dr. Neil Kumar:I don't know
Dr. Moira Gunn:if it's but but if anybody's worked in a large organization, you see that the organization thinks it owns all the resources. Where the the resources are interchangeable and and supportive. Great. Those are those you're working at the BridgeBioPharma level. But then in the various companies, you got a hard time saying, hey.
Dr. Moira Gunn:You gotta give me your guy. It's like, no. I don't. I got my old company.
Dr. Neil Kumar:Yeah.
Dr. Moira Gunn:I think we're really speaking to something that breaks through what has been the traditional idea of a corporate structure.
Dr. Neil Kumar:Well, I mean, I think it's important that you say that there's a a wonderful book, that was written by, Jeffrey West. He's the president of the Santa Fe Institute called Scale. And he goes through and he just he he tries to analyze every single thing on earth, basically, and understand why it tops out at a certain size. Right? So certain things scale, like, you know, x to the 3rd, but, you know, you can you can only transport over, you know, let's say, x.
Dr. Neil Kumar:And so, like, there there'll be limits to the size of a human, for instance, or the size of a city. And what he finds is if for corporations, what happens is as you get larger, you try to centralize as much as possible because you're going for economies of scale. But that centralization in and of itself is what prevents new innovation, which tends to flourish in decentralized models. And decentralized models have a different property, not economies of scale, but returns to scale. They actually get bigger the larger they get.
Dr. Neil Kumar:And and most companies are economies of scale centralized, and ultimately, most companies aren't along around for a long time. Right? The biggest companies today are not gonna be around 30, 40 years from now. But if you can keep them decentralized, you keep that innovation engine going. And then the challenge that we have right now is how do you marry that with something like commercial, which benefits much more from centralization.
Dr. Neil Kumar:And we're gonna have to solve that, on a go forward basis, but it'll be in, you know, sort of an interesting corporate experiment.
Dr. Moira Gunn:So at any rate, you've got this broad portfolio of disease areas. And so let's let's go across those diseases because it's 1 thing to say, well, all the genetics and all the problem. But you recognize a lot of of diseases going across the disease area.
Dr. Neil Kumar:Yeah. Exactly. So, I mean, I just give you some examples of our later stage programs, but 1 of the earliest forays, we made was into the area of precision cardiology. And, cardiology is almost where today cancer might have been 20 years ago in the sense that these broad diseases like heart failure or heart failure will preserve ejection fraction. We're now realizing our different genetic subpopulations.
Dr. Neil Kumar:And I had done some work on that, as a venture capitalist before, and so 1 of the areas that we wanted to get involved with at the start was an ATTR cardiomyopathy. So here's a really good example of what I'm talking about with well described condition. You have in all situations, a destabilizing mutation in a tetramer in your blood. And every single time a patient has that destabilizing mutation, they get this disease. Right?
Dr. Neil Kumar:And all we're doing is we're restabilizing the destabilized tetramer. So that is genetics telling you what's causative and ultimately the ability for a small molecule therapy in this case to reverse the causal driver of the condition. You know, analogously, in achondroplasia, which is another condition that is the most common form of dwarfism, you have a gain of function mutation in a receptor and there we're just inhibiting that gained of function with a small molecule inhibitor. So again, a very very straightforward therapeutic hypothesis. It almost tells you how robustly we understand the disease.
Dr. Neil Kumar:So it's like every time you have the disease, in the case of ATTR cardiomyopathy or the condition in the case of achondroplasia, you know that it's being driven by this thing, and we're just basically trying to take that thing that's driving it and and reverse its effects.
Dr. Moira Gunn:Now you said small molecule. It means you're going after pills. Just simple pills that people can take. Is that part of the plan? Try to get it into a small molecule?
Dr. Neil Kumar:Yeah. It's a it's that's a great question. So, like, we we we say, a bridge that we're a modality agnostic, meaning we'll use a small molecule. We'll use an antibody. We'll use a gene therapy.
Dr. Neil Kumar:We'll use that on an enzyme replacement therapy, but we'll use anything that allows us to get most quickly to the marketplace and serve patients most productively. So in some cases, that is a small molecule. In many cases, it's a small molecule because bridge kind of goes after the things that are overlooked by everyone else. That's what we pride ourselves. We're like, you know, the underdog people.
Dr. Neil Kumar:So, you know, small molecules are not sexy anymore. Gene editing is sexy right now. And so if you're gene editing, you probably can find funds to push it into the clinic. But if you've got a small molecule that can really reliably serve patients, chances are not a lot of VCs are super excited about that. That's where we come in.
Dr. Neil Kumar:So we have probably have 80% of our portfolio small molecule, but we do a good deal of gene therapy as well. And, really, it comes down effectively to working from the marketplace backwards and saying, what is ultimately the right way to solve this condition? In the case of TTR, we believe it's a small molecule because it can address the destabilization of a tetramer, but it keeps the tetramer around, which is an important thing. In the case of congenital adrenal hyperplasia, which is disease we work on, which many of your listeners may not have heard of, but is a very common inherited disease, gene therapy is the only way we can think of going after because you're missing something inside the cell. And it's really hard with a small molecule to pick up something that's missing.
Dr. Neil Kumar:With a gene therapy, we can provide that inside of the cell. So it really comes down to the biology and then what we could do for patients that's that's differentiated. And and, yeah, that's how we that's how we choose the the mode.
Dr. Moira Gunn:I love how sometimes you're like, oh, yeah. I'm I'm a venture capitalist, and I do, you know, and I do this. And sometimes you're like, they, those venture capitalists over there. How is being who you are as both, how has that evolved with your experience here with Bridge Biopharma?
Dr. Neil Kumar:Well, I was very lucky to to, sort of join the industry and, to join within the context of a firm. It's called Third Rock Ventures that I think was really doing wonderful things for innovation and patience. But in all cases, I I would say that when you're working inside of some system, in this case, venture capital, you see both the benefits and the limitations. And the limitation as compared to a company construct like we are is first and foremost that a venture capitalist needs to take something on and then sell it at some point to the public markets or to pharma. And hedge funds need to obviously avail of some catalyst or some uptick in valuation that occurs on, let's say, a yearly basis or a biyearly basis.
Dr. Neil Kumar:But what can a company do? A company can step back and say, I'm on a 14 year journey here, right, from start idea all the way to marketed product. And how do I assess that 14 year journey? I do it through the veracity of the sciences, the high probability technical success high enough. And I do it through trying to understand what the overall value of the program is.
Dr. Neil Kumar:And I think that venture capitalists get caught up in small bunches of value, which therefore drives them to inefficiencies that if they were hanging on to the program for all 14 years, they wouldn't necessarily do. So let me be specific about that. It's like, you know, when you're out here next, you could drive down the freeway. We call it the 101 out here between the the burbs and and downtown San Francisco, and you see all these big buildings. Right?
Dr. Neil Kumar:Big signs. And many of those companies are not that large, but they are spending inordinate amount of money on, like, a really nice facility.
Dr. Moira Gunn:Yeah. The size.
Dr. Neil Kumar:The size, the facility, all the and why are they doing that? It's not silly because everyone's doing it, so there must be a reason. The reason they're doing it is that's kind of a biomarker of success. It's like, oh, wow. We can't we are a big company.
Dr. Neil Kumar:We can go public. It looks great for investors, and therefore, investors are able to make money on that, and they're able to do good science too. But if you really just cared about the NPV, the net present value, how do I most efficiently move the drug from a to b, b being the marketplace? You wouldn't sign up all those big buildings. You take a low slung lab like we have somewhere near Palo Alto, and you try to get the minimum number of people that just work on it.
Dr. Neil Kumar:And if it didn't work, you'd kill it and move on to the next project. But in the case of a single asset company or a company that only has a couple ideas, they never really wanna kill that idea. So you have a lot of inefficiencies that derive from that system that otherwise is a really positive system. But that that that's why I say sometimes us, sometimes I say them, because I sort of straddle those those 2 worlds.
Dr. Moira Gunn:Well, you're either gonna be embraced by both or rejected by both. So good luck to you, Neil, on that. But anyway, the, now you said something earlier about, you know, out there getting the data, data out there, putting it together. You know, There's a whole lot of data going on at Bridge BioPharma, and sometimes that data, a lot of people can use or multiple people can use. Other times, no, it's very specific to what you're working on.
Dr. Moira Gunn:Let's talk about that. How do we get the data we need to solve these genetic diseases?
Dr. Neil Kumar:It's a great question. Actually, it begins with not us. It begins with the wonderful work that's occurring, that the NIH has funded, that MHRA and others have funded, outside of the US and in places like the UK and elsewhere, and the wonderful work that's being done in academia. So the data that's occurring there is effectively the genetic data, so what is it that is driving disease and these big databases that I alluded to earlier. And it's also the elucidation of a mechanism.
Dr. Neil Kumar:So a great academic will be looking at a disease, and they'll spend 10 years trying to figure out precisely what are these mutations doing. And it's really at that moment where they understand what the mutations are doing and they understand how important the genetic signature is for this disease that we become involved. So that's the first batch of data. We don't we don't create it. All we do is we look at it through subscriptions to databases, through 22 university partnerships, and a lot of my job and everyone else's job at this company is to just go out and visit academics and talk to them about what their idea is to solve condition x or y, which makes the job just absolutely wonderful.
Dr. Neil Kumar:It's a like, that's that's a great that's a great job. Then the data that we generate has to do with how do we manipulate the system to make it better. So that person, the academic, let's say, he or she has defined the playing field. And now we're coming in and saying, well, how do we change the playing field so we can better the patient? That starts with data that's preclinical in and around cellular biology, mechanism goes all the way to animal models.
Dr. Neil Kumar:And then, obviously, the second big piece of data generation is clinical data generation, that that we that we take forward. And that kind of nicely ties back to the genetics because we're sequencing all of our patients, trying to understand whether our understanding of the genetics that we started the program with continues to hold up in the context of therapeutic intervention. So that's that's the cool part is is really a lot of the data that we're that we're working with is data that's coming from, you know, the geniuses of of whose shoulders we stand on.
Dr. Moira Gunn:Now you did say to me earlier, though, that while we all think that these scientific researchers at universities, in in academia are really doing the the drug discovery. That's not really true.
Dr. Neil Kumar:Yeah. Well, you know, drug discovery and development is, like, the biggest team sport I think I've ever seen. We talk about this concept of a swarm in, at BridgeBio. It's it's kind of like, it's it's it's, you know, it's it's sort of like there's no 1 individual who can really understand everything that's going on all the way from, you know, sort of basic preclinical biology all the way through, getting a drug approved. So what I mean what I meant by that is academics do a very good job typically of understanding the disease condition.
Dr. Neil Kumar:What they are not trained in doing is actually creating the chemical molecule, the small molecule or the gene therapy, that ultimately is the intervention that's gonna get into the clinic. Now, you know, so so the majority vast majority of drugs, those are coming from companies that have those skill sets. Right? Medicinal chemists and and others and expertise in dealing with the regulators, etcetera. But what that doesn't mean is that the core idea, let's say someone elucidated this mechanism or this pathway didn't come from academia.
Dr. Neil Kumar:All I'm saying is it's a team sport. I think without academia, BridgeBio would be nothing, And, hopefully, the academics we partner with would agree that without BridgeBio, the ultimate manifestation of their dreams, which is a drug that's helping patients wouldn't have necessarily been as easy as well. So it all works as as we all come together.
Dr. Moira Gunn:So in a sense, yes, all of those scientists are out there figuring out the science. What's wrong? How does it work? And then you go, well, thanks. I think we can we might be able to build a drug for that.
Dr. Moira Gunn:Now you've gotta do more science to make that work, but it's like it's 2 different things. It's 2 different things in a sense, but together. Yeah.
Dr. Neil Kumar:There's actually 2 interesting, things to mention here. 1 is that universities over the course of the last maybe 15 years started to realize that they too could productively be involved with the early stages of drug discovery. So you've seen some absolutely wonderful institutes arise like, Dana Farber has 1, MD Anderson has 1 that we partner with where they actually take ideas from some of the academics and actually do some of the early chemistry themselves. And then they'll license it out later to, to a pharma company. So that's that's 1 trend that I think is worth paying attention to.
Dr. Neil Kumar:The other trend that's worth paying attention to is the fact that with newer modalities like gene therapy, academics are actually able to take it further inside their own labs. So for instance, when we partner with, a luminary like at a University, Massachusetts Amherst. He's already advanced to gene therapy a year away from the clinic, whereas if I took on a small molecule, it may still be 3, 4 years, away from the clinic. So there's some really, really neat
Dr. Moira Gunn:And when we say away from the clinic, we mean first in humans. We're actually gonna try it in humans.
Dr. Neil Kumar:1st in human, which is another 5, 6 years from the marketplace. So, I mean, the timelines you're talking about here, that's a good it's a good reminder. You know, an academic could work on a disease for 20 years and really crack it, and then we come in and we'll work on a drug for 10 years. And together, that process allows for a marketed product maybe some 30 years later. But but, you know, that cycle time is accelerating the more and more we have all of this information that describes what's happening in a molecular level.
Dr. Neil Kumar:So that that's the exciting thing about today.
Dr. Moira Gunn:Well, I have 1 question, and that is it sounds funny, but because we know that Bridge Biopharma is publicly traded. If I buy a share of Bridge Biopharma, am I, are I getting parts of those other companies? How does that work? What does that mean?
Dr. Neil Kumar:It's a great question. Yeah. So we effectively wholly own these companies now. So, yeah, it's it's it's almost like having a drug portfolio. It's just that we continue to use the company structure so that we can provide incentives at the level of each program.
Dr. Neil Kumar:And what that means is having for reasons that we don't have to get into, but for for legal structural reasons, it allows me to say for my employees that are working on, say, pantothenic kinase deficiency, they'll only gonna get rewarded if that drug advances, but not necessarily if my TTR drug advances. And the reason that that's important is that that they really focus on what they're doing. It's focused at the level of their biology, and it takes away from this sort of, I would say, confusion that you get in large pharma where, yeah, I'm working on this project, but it doesn't really affect my, you know, my my overall compensation, in a in a meaningful way. This this this aligns all incentives very well.
Dr. Moira Gunn:Well, doctor Kumar, this has been terrific. You know you're always welcome on TechNation. I hope you, come back and see us again.
Dr. Neil Kumar:Thanks so much for having me. I really appreciate it.
Dr. Moira Gunn:Doctor Neil Kumar is the founder and CEO of Bridge BioPharma. More information is available on the web@bridgebio.com.