John Simboli:
0:00
Welcome to BioBoss, Ryan.
Ryan Beal:
0:02
Thank you, John. It's great to be here. Great to be with you,
John Simboli:
0:05
Ryan. What led you to your role as CEO at Dyve Biosciences?
Ryan Beal:
0:09
I'm a physician and scientist by training. I have my MD, but I never practiced medicine. I got sucked into the industry side of medicine early in my career, on the management consulting side, and really enjoyed that, and got exposure to, you know, really big problems at really big companies, and I think helped create a number of really good strategies and suggestions. But ultimately, you know, I was an entrepreneur in my heart, and I wanted to lead something, and I wanted to do more than just solve the problem and hand you the solution and then go on to the next one. I wanted to really create something. And so, you know, I got to work thinking about what I wanted to do on the entrepreneurial side in life sciences. And, you know, one of the things that drove me to Dyve was, you know, I've always been focused on where are the bottlenecks or where is there a problem that man if I could just crack that I think it would really open up something. And that's what I saw as we were kind of incubating the early ideas behind what became Dyve. The biology was strong. The molecules were strong. It was that delivery link that was broken,. And I thought, man, this gives me the chance to really build that bridge instead of writing another paper about it, or instead of writing another PowerPoint deck and handing it over to the CEO of some big company. So it was really about just owning the science and wanting to build something. And it's why we built the company, and it's how, you know, I've approached it. And of course, it's changed through different phases of the company. What excites me, but the core of where it got started was really wanting to create something that solved the bottleneck.
John Simboli:
1:58
I was curious about when did you know that you were an entrepreneur?
Unknown:
2:03
When did I know? Probably came later, you know, probably in my college years when I realized it. But when I go back now with the perspective of being a parent and talking to my parents, I was an entrepreneur, kind of out of the womb. And you know my parents will tell me funny stories, and when I look back, I say, "Yeah, you're right." I mean, the most crystal clear example to me is, you know, I grew up in a relatively small town in Colorado, and you know, a lot of kids have lemonade stands. You know, you start a lemonade stand, you make a couple bucks. And in second grade, I decided to start a spinach stand. And I just saw the other kids doing lemonade stands. I thought we're growing spinach in the garden. We like spinach. Other, you know, Popeye was a big thing then. I said, let's I'll do a spinach stand. And you know what? It worked great. It took off, and that was kind of you know that became a summer staple for a couple summers. And that was kind of my first entrepreneurial experience. But then I started a lawn mowing business, and I know you're in the New Haven area, so you you get the seasons. I'm in Southern California now, so I don't experience the seasons, but where I grew up, you had the seasons. So in the summer, we were mowing lawns, in the fall we were raking leaves, in the winter we were shoveling snow and clearing driveways. That was probably my first real business, and that was before I had my driver's license. You know, so I was probably 13, 14, but started a business, started hiring my buddies. Called it Able Adolescent Associates. And we picked that name because it was going to be first in the phone book. Of course, this is still, you know, no online stuff at the time. But I've always kind of had that entrepreneurial spirit. But again, I probably didn't really think of it that way until I was older. But looking back, it's definitely a through line from when I was early elementary school days.
John Simboli:
4:11
When you said to your family and your parents and those your loved ones that you were starting off, perhaps after the consulting, and striking out on something with no clear definition, how did that go?
Ryan Beal:
4:23
It was interesting because I Igrew up had a you know essentially with a single mom in Greeley, Colorado. And she was a teacher by training. She worked in school administration while I was growing up. She had a very just supportive approach, and I think didn't push me in any direction, was more a explore your interests find your passion let you get, you know, you're going to get tugged in a certain direction and I'm going to support you whatever that is. There were no physicians in my family, so, and no scientists in my family. And so I think that was interesting to everyone. I had a real passion and draw to math and science, and and loved it. And I think what connected with me very early was not just the math and the science, but it was more that problem solving approach. Like I just, you know, in math, I loved figuring out a problem, so I was the the math nerd in school, was on the math team, all those kinds of things, and in high school, is you know did science fair. But I just loved trying to figure something out, and that's you know that's a big part of what drew me into science. And then, of course, like a lot of kids, you know, I had a very influential high school biology teacher that was, you know, when I look back, probably, you know, the most important kind of teacher in my early days of schooling. Her husband was a family physician, and when I was in high school, I kind of said, "Yeah, that, I want to be a physician. But then to get to your point, as I got into further in my schooling and training. You know, one of those critical kind of forks in the road for me was medical school, and I happened to be in Philadelphia at Penn. And you know, the med school's on one side of Spruce Street, Wharton's on the other, and I started taking classes at Wharton. And that kind of, that problem-solving thread, that anchor of problem-solving, pulled me more into the business side of medicine. And so I had this kind of foundational science knowledge and interest. But the problems that were being solved on the business side were very interesting to me, and so that is kind of what initially sucked me in. And I think a lot of my family was, part of my family was relieved, not relieved, but definitely not, didn't have angst that I wasn't going to be a doctor. And the other part was, well, this is interesting. He just spent a lot of time and money in medical school. What's he doing? But I think it does go back to kind of my mom just giving me the flexibility from a very young age to explore interests and let my interests kind of guide my development, if you will. And I got sucked into the business side of medicine, is how I say it. Well, and a big part of that, John, too, is you know of course when I was thinking about this, you know I Ikind of jokingly said everyone's wondering, you know, he just spent all this time and money in medical school and now he's not going to use it and so but I struggled with that same question of course like you know is this, is this really the right path? Am I making a mistake? And initially, when I made the leap into, at the time, management consulting, the way I got comfortable with it is I said I'm going to go do this for a couple years, and I viewed it as kind of getting my on-the-job MBA, understanding the business side of medicine, and then I was, my plan after medical school was go do that for a couple years and then come back and go through. I wanted to be an orthopedic surgeon. Sports has always been a big part of my life too, and so I wanted to be a sports doc. You know, do knees for you know or shoulders. I thought I'll go get my on the job MBA for a couple years and then I'll go back and practice medicine. And then a couple years came and went a couple times, and I just I really enjoyed what I was doing on that side. And ultimately, well, I missed, I really missed, especially early on, the patient interaction. I mean, I love just dealing with just, you know as a physician, you deal with all of society, you know, all different demographics, all different socioeconomic tierss. And I really did enjoy that, and I missed it early on. But ultimately, kind of at least how I rationalized it or got comfortable with it is I felt, for my skill set and my interests, I could have a much bigger impact on medicine on the business side, and trying to solve some of those bottlenecks, and inin particular, translation bottlenecks, and bringing great ideas out to patients. And then rather than than doing two surgeries a day, and then seeing eight patients in clinic the next day, I could do something that impacts hundreds of thousands or millions of lives, or play a key role in that, and that was really kind of self-inspiring.
John Simboli:
9:27
So let's look at the management consulting link between interest in science, studying to be a physician, and then becoming a full-fledged entrepreneur. I guess you're always full-fledged once once you're an entrepreneur. But anyway, let me think how to say that. So, in management consulting, that it can vary, of course, depending on what sector you're in and who you're with, and all those different things. But it can be the case that consulting is, ithas shorter timelines and more defined things, and you move quickly from one. Whereas in biopharma, there are pivots, of course, but it's a long cycle. So, how did you take that one experience and then apply it to the other?
Ryan Beal:
10:09
Great question, John. I mean, I, at the time, and even now, retrospectively, look back at my management consulting days as as a boot camp for a non-business-trained person, a scientist and MD by training, to just learn what's important, and that fast pace, the exposure I got to senior executives and sitting in boardrooms, and seeing the implications of different moves they made strategically, both scientifically and in the capital markets, and then going on to another project, you know, a month later or two months later. It was just this very rapid cycle of learning and development, and that's what I took away from management consulting. It's just a incredible intellectual development. Like I was just really lucky to have, you know, just crazy experiences as a 20-something sitting in boardrooms of Fortune 100, you know, some of the largest biotech and biopharma companies, right with their, with their board and and C-level executives, just sitting there, And and they're looking at me, asking my opinion, and I'm, and you know I just said this is wild, this is crazy, but such a good learning experience. The other thing that I learned, and but I don't think this is unique. I was able to see at a very young age that these other executives weren't that different, you know. They had more experience, but they were just people, you know. I think, especially growing up in a small, smaller town where I did, and you know, I wasn't exposed to C-level folks, and so in my mind, it's like, whoa, that's an extremely elite tier, and it is. There's no question, but when you sit down with them, you realize we're all just people. We have kids, we have families, we have struggles. You know all these things. They're just people that are also making extraordinarily impactful decisions on a daily basis. But that was really eye-opening for me, and I think kind of opened the aperture of what I thought was possible for me. So that was kind of the what I took out of management consulting was just a lot of development at a really critical point for me in terms of just from an age perspective and just intellectual development, you know, your brain's just soaking up everything. It really just set me on a a real cool path.
John Simboli:
12:49
Sounds like from what you just described, the ability to be around really bright people who could understand multiple layers of things, the science, the capital markets, and so forth. They were probably frequently in the business of making a switch to make something work better, and I'm wondering whether that process of being ready to pivot, mentally being ready to pivot, has been useful as, you know, at Dyve and in your work in biopharma.
Ryan Beal:
13:19
You know, as a management consultant, you're jumping from one problem to another. A different company, one may be, you know mergers, mergers and acquisition study. The next may be drug development, but you know portfolio prioritization. Another may be sales force execution. So you're just you're constantly challenging different ways of thinking and working with, you know, a different type of team with different motivations. And so that's kind of one level is just the different kinds of projects. But then the other is, is just seeing at a more granular level the pivots that they make based on, you know, the most recent data or based on what a competitor is doing. And so there's that there's kind of the external pivots, company to company and functional area by functional area, and then there's the internal kind of strategic pivots, and that's been very very helpful. You know that was helpful kind of foundational knowledge to acquire at a young age, and then but I put it to work all the time, especially in a startup. I mean you have to be, you have to be ready to pivot. You have to be ready to focus on let the data lead you, and things change, you know, as you get more information, and you you can't stick to what you originally thought.
John Simboli:
14:32
Can you tell me, you know, how you conceived as the co-founder, what what drew you to that? You were beginning to tell me that at the very beginning. And then what did you think you had, and then what did it evolve to realizing that you had?
Ryan Beal:
14:45
What originally drew me to the idea was, again, if I get back to kind of what are, I like hard problems, I like things people haven't done before, and even better if they don't think it's possible. And the core idea of where we got started is you could, this concept of what if you could take a molecule, a drug, through the skin, do it with the speed of a needle and the bioavailability of a pill, but avoid having to jab it in or take something orally. And you know the dogma in the space would say you really can't do that. There's a small subset of drugs that you can do, you could do that with, and we all know what you know examples of those typically driven by a patch. But those molecules are always, they share common characteristics. They're small, they're moderately fatty, and and they're very potent. And what drove me to this was people just said that's kind of where the line's drawn. And at the time of the founding, one of my my co-founders came to me at the time, we were just colleagues, you know, not connected professionally, and but he was an ophthalmic surgeon by training, and he had been working on drug delivery for a number of years, and but related to the eye. And he started thinking, he was a a polymath and one of these guys that could really just connect these disperate dots of information and he just really thought that he was onto something with skin penetration and he was showing me a bunch of theoretical approaches to do it and he had a lot of conviction that it was going to work. You know, you kind of take a leap and you say, I don't know. This sounds out there, but if he's right, this could be really, really interesting. And if he's wrong, hey, you can't hit a home run if you don't swing the bat, you know. And so I said, this is interesting and worth exploring. So that's kind of where it started. Was just that intrigue of man, if we could avoid a needle, this could be really interesting. But at the time, to get to the second part of your question, what I thought I had was, hey, we'll have a very differentiated approach to skincare. We'll be able to drive molecules deeper into the skin, and we'll have a neat little skincare company that's based on science, not based on marketing. You know, we'll let the science do the marketing for itself. Very early on, we realized, you know, like a lot of these things, it's you're surprised. Something happens. It's just like you say. You pivot. Well, we realized we were as we were doing some testing of these molecules, not only were we getting them deep into the skin, but we were detecting blood levels, serum blood levels, and that was a real pivot point for the company where we all realized, okay, this isn't a skincare company. We have a potentially quite revolutionary drug delivery science that we could leverage into therapeutics, and that was a big shift for the company, and ultimately drew me into the oncology space.
John Simboli:
18:18
The focus on helping people with cancer, maybe you could just walk me through how you got that realization. This is where I want to take this potentially remarkable idea and apply it.
Ryan Beal:
18:30
Let me answer the specific tumor piece. I mean, tumor acidity has driven cancer biology for two decades, and we've known tumors generate, that they generate and thrive in an acidic environment, for 100 years. Otto Warburg discovered this and won the Nobel Prize for it in the 1920s. So we've known about this for 100 years. For the past two decades, we've known that if you can correct that acidity, you have profound downstream effects, beneficial ones. I looked at it as look, we've known about this for decades, even a century. We've certainly known for decades that if we fix it, it helps tremendously. So I frame it as the science was settled. What was missing was translation. It was just this, a way to modulate in humans safely and at scale. That piece was missing. You could do it in animals beautifully, but human biology made orally delivered approaches not workable. It made injectable approaches not scalable, and so that's what we built. We said we've got a way to solve that translation gap. If, you know, assuming we can get that drug in through the skin, I think we've cracked a major node in cancer, and that's what we've done. So we've built that. DMAX is our delivery science. Now we've already validated it in a phase two study in inflammation and acute gout, and DYV 800 is our oncology asset. We're basically, we're saying, look, we and others have shown in animals that if you correct pH, it's a very upstream regulator of all these downstream pathways. If you correct that, turns back on the immune system, potentiates a number of other drugs, et cetera, et cetera. It's very powerful in animals. We've shown in humans that we can deliver it, and we can, and the the target engages. pH is druggable, and so now with our oncology lead, we're showing that hey, we can take this animal biology, we can marry it to the human delivery that we've shown in an adjacent TA, and let's see if we can do both now in humans, the cancer biology, the human delivery, and really be a rising tide that raises a number of boats in cancer. I mean that's the hope. So it's bringing that same mechanism into first in human studies and oncology later this year with Moffitt Cancer Center down in Tampa. That's that's the goal, the near term goal.
John Simboli:
21:11
Is it too early to think to yourself? You know, this would change the lives of patients.
Ryan Beal:
21:16
It's not too early, John. I mean, that's what motivates me and the team every day. I mean, we've all been touched by cancer, either directly or through family. You know, I'm a cancer survivor. My mom lost her life to pancreatic cancer. My dad lost his life to AML. You know, it's we've all been touched, and you know what we're working on is such a foundational root cause, a first principles issue, tumor acidity, and we've shown, again, in animals that it's druggable. We can change that pH, and when we change that, we can measure the downstream effect. And so, as I, it's extremely motivating, John. That's what keeps us going every day. And I, what interests me personally about it, I mean, there are multiple things, but at its core, the biology is understood, well understood. The chemistry is very simple. This is high school level chemistry, changing pH, delivery has been the challenge, and that's what we're unlocking. And so I like the simplicity, you know, solving a very complex problem, but with something that's very simple, and that patient impact. I mean, the ultimate hope is that the studies will support what we've seen in the animal models, and by addressing that foundational tumor pH, you really become a rising tide that raises all boats. And I think that's where the real power is here: is we're not seeking to be the next monotherapy drug that fixes. I think the real power is if we ultimately see in human studies the benefit that we hope to see. All of a sudden, we become this rising tide that raises all boats. The immunotherapies become more effective. The ADCs become more effective. Chemotherapies, and that's what really excites me. The patient that goes in to treatment today and gets to the point of not having any more options, you know, in 10 years they have hope. You know, it's ultimately measured in response rates and survival and all those things. But that rising tide is what I, that's what we're after.
John Simboli:
23:45
The word that came to mind while you were telling me that just now was elegance. I guess that's a word that scientists and mathematicians use when they find something striking that is remarkably simple on its face, but transforms.
Ryan Beal:
24:00
Yeah, and that's, I mean, again, going back to my even my early days, but just also as a clinician and scientist, I mean, a lot of innovation happens, and you know from your background too, and a lot of great innovation happens in a pathway-specific development. And you see this in, I won't say every therapeutic area because I'm sure there are examples where this doesn't hold. But you see this broadly. I'd almost call it scientific silos. And our system, just from education to postdocs to drug development, you know, you become an expert in not even a pathway, in a specific protein at the end of that pathway, and that's great and leads to a lot of incredible innovation. And where what we're doing is trying to go upstream of those pathways and really modulate the ecology of the tumor itself, the environment around the tumor, and allow those pathway targets to work more efficiently. And that's what excites me.
John Simboli:
25:12
When you took this idea, which is quite different, sounds like, from what other people have been trying to do. I'm sure you got plenty of, well, this is such a good idea, how come no one did it before, kind of stuff. So, how did you work your way through that?
Ryan Beal:
25:26
Oh man, John, I've been punched in the face a lot of times, and I think there are kind of two forces at work here, and both are brutal. Both create a heavy current that we that we had to swim against. And one is the topical approach, that's one, and then the other is just that pH itself is is druggable. And so when you really believe in something, and then you start seeing the data merge, and again, there's changes along the way, of course, but you start saying, oh, this is real And scientists see this all the time. Little pieces of data, you know. Ultimately, things may culminate in a study or a peer-reviewed published paper and things like that, and that's great. But there are a lot of steps along the way, whereas a scientist and as a team, you're getting information and you're saying, okay, it's working, or hey, we need to change this and it'll work better. But as you start to internally gather that momentum, it gives you more and more confidence, and you kind of get to this point where you just say, you know, I'm going to let the market catch up. B e c ause they'll catch up, and I've go to, I can't convince them without the data. The data is going to take some time, and it's got to, you know, withstand a lot of different pressure testing. But given time, I'm going to get them there. And at the beginning, again, I've got these two big forces against me. I mean, we were met. It kind of went in stages, and I would say the first stage was more cynicism, not even skepticism. Just like you're crazy. You can't. You just can't do it. There's no way, and you kind of work through that, and you work into the skepticism zone, where they're still, they're still not buying it, but they're like, oh, your data's intriguing, but you need to do this model or that model, or. So you continue to work, and I still face a lot of people. I think we're kind of through. It's definitely beyond the cynicism stage, but skepticism is great. I was skeptical, like we said, just from the very beginning. But those skeptics, once you convince them, also become your biggest champions, and that's what we're starting to see now is you know, just through my network and colleagues, have had the same conversations with the same people over the past six,, eight, 10, years about what we're trying to do. And I've seen that transition from cynicism to skepticism to holy cow, yeah, you guys said you were going to do it, and you're doing it. And it's they become your big big champions. So, you know that resilience and perseverance, and like I said, being punched in the face a number of times and hearing no or hearing it's impossible. You have to listen. You have to listen to why they're saying that, and you have to understand why they're saying that. That's all important to learn. But if you have conviction and you're starting to see confirmation of that conviction. You keep going, and that's what we've done.
John Simboli:
28:47
When people think that they have understood what Dyve biosciences is about, but perhaps they've misunderstood because of preconception or just a different way of looking at it, what do those misunderstanding tend to be? How do you bring them back into where you really are?
Ryan Beal:
29:04
What people get right is the science of tumor acidity. They understand that. What people get wrong is the assumption that anything topical is a consumer story. You know, topical carries baggage. I've learned, again, this is through many of these conversations that we don't apologize for it. You know, topical carries baggage. It is what it is. We just bring the human data, and that, again, was something that we and I had to learn over time. I wasn't going to convince them that our delivery science was amazing without human data. So we said, Okay, we're going to go get the human data. Once people see our phase two gout results and the framing shifts. It's okay, you have done something here. And then they start digging. Then they'll look under the hood. But it took getting that phase two data for people say, okay, it's real. Now what else have you done? And then as they start to see the different branches of what we've done, those branches are more powerful now. With the trunk being the human data, if you will, it took a lot of time to build those various branches, which are on a range of different molecules, range of different models, all those things. Any one of those, I should maybe say roots, not branches, but any one of those roots alone was easy to dismiss from an outsider. It gave us internal confidence that we're headed in the right direction, but they were just the roots. It wasn't enough. You couldn't lean on the tree. And now you've got the phase two data. People say, All right, what's under the tree? But I think that's really important, is, you know people understand the science of acidity, they understand that the biology is there if you can correct pH. They've questioned whether you correct it, and topical carries baggage. So we've said to answer both of those, we're just going to bring the human data. We'll let the data, the pharmacodynamics, speak for themselves. You can't deny it. So that becomes something where then they say,"Okay, let me see what's next. If we led with topical, immediately dismissed. You know, there's this, there is again just dogma in biotech and pharma, biopharma broadly, life sciences that serious drugs are injected, patient-friendly drugs, oral, and they can also be efficacious. But if it's not injected, infused, or in a pill, it's not, it can't be serious. And so we started saying, Well, let's just show them the data. We'll come back to the delivery later. But you stack the data up and you say, 'This is what we've done. This is what we've done. This is what we've done. Here are the results. Well, how does it work? Well, here's how it works. We're engaging, we're modulating pH. pH is the target. Okay, interesting. What . . . if you never mention the word topical? The reaction is this is incredible. So you kind of bury the lead. And we were so excited early on about the delivery science. Oh, this is an innovative approach. People, if you could avoid the needle, this is wonderful. But you realize through trial and error that that baggage can often just shut down a conversation. That topical baggage. But if you start with the data, say here's what we've done. Now let's get to how we did it, later. People will engage. Oh wait, so it's topical? Yeah, it's topical. In fact, it has to be topical. You can't deliver it another way. That's the positioning that has kind of evolved over time. But again, it all links back to just bringing the human data.
John Simboli:
32:55
Having insight is rare enough to be a leader, and then being able to convince others, for instance, investors to to come along with you, that's rare. To be able to build a team, that's a whole separate skill, right? And not necessarily easily taught. So, how did you learn how to build a team?
Ryan Beal:
33:13
I've always been very focused on team, whether it's professionally, you know, I'll say personally or athletically. You know, I grew up playing sports. I've worked with a lot of athletes professionally, professional athletes, but but also just in a professional environment. And I've just seen in all aspects of my life how important team is. Could be your team at home, could be your team at work, could be your football team when you're a kid, but team has always been something that's been a big focus of me. I've always take a lot of joy and in development of team, both personal development, myself, but also developing team members. Big believer in bringing the best and trying to find people that are smarter, better, faster than me in every dimension. But I think my role is to assemble that team. And even when assembling the team, I'd like to think I'm fairly adept at it. You know, the famous quote, you can go fast alone. You can go far with a team. And that is so, so true. I mean, I take great pride in our team and what we've built, and very collaborative environment, very non-hierarchical. You know, people, have an obligation to dissent. Some of our best ideas have come from the most junior people, and that's expected. If you don't, agree, I want to hear about it. I want to be challenged, and together we'll work it out and we'll get to a better answer. But the last thing I want is someone sitting there internally thinking this doesn't sound right, or what if we did it this? I want to hear it, and let's bat it around. Let's push it around a little bit. And motivated by things that ultimately can translate to the patient, and built the team very focused on that impact, the patient impact, and that's what motivates us all. So I think that underlying motivation, everybody got.
John Simboli:
35:20
Thanks for speaking with me today, Ryan.
Ryan Beal:
35:22
I really appreciate it. I enjoyed the conversation.
