Achieving The Impossible In Curing Congenital Heart Disease, with Timothy Nelson

Dan Sullivan: Hi everybody, this is Dan Sullivan, and this is the next episode of the Free Zone Frontier.
 
Tim Nelson: Yeah, so Steve and Dan, thanks. It's great to meet you, Steve, and it's great to be with you again, Dan. I'm just a kid from the Midwest. I grew up in a family, a farming family, and my stepdad was a physician, family physician, and I grew up in a farming community, but also in a physician family that did house calls and did all that standard primary care. He was a general practitioner, which did everything. And I went through my life- I got my first job at 16 on a factory floor, and I got fed up in 24 hours and quit my job and started a window washing company. So I've always just kind of had that "I don't like working for anyone else" type of mentality. And then-
 
Steve Krein: You're starting to sound like Joe Polish now and window washing/carpet cleaning.
 
Tim Nelson: Yeah, a little bit, little bit.
 
Dan Sullivan: Yeah. He's in Joe's clutches already.
 
Tim Nelson: So with that kind of spirit in my background, I got also frustrated by medicine. As I went through medicine training. I got kind of annoyed by what was in the textbooks. I got fascinated by what was not in the textbooks. Every doctor would tell you 50% of what they learned in medical school was wrong, things weren't changing that fast. So I ended up making a decision to do my PhD and I was a slow learner. I did the MD PhD track and I ended up being enamored with what wasn't known and what needed to be developed to be able to transform medicine and focus on the problems that existed. And medicine just became so palliative in so many ways that we just fixed the problem, we put a bandaid on things, we gave a medicine to alleviate the symptoms, and there really wasn't a curative approach.
 
And that was always innately frustrating. And I enjoyed my PhD, developmental biology, regenerative medicine field. And then it's amazing how life works. As a graduate student, Shinya Yamanaka and Jamie Thomson discovered induced pluripotent stem cells, and that was in the Bush era of the embryonic stem cell debates of the world. And then IPS cells suddenly became the solution to no embryos made or destroyed, and had all the potential of pluripotent cells. And so that was really at a very informative period of my career where I said, "Why not? Why not use this technology? Why not use this to fundamentally cure diseases?" And the disease that I became passionate about is congenital heart disease. So, fast forward through my medical training, my residency, my fellowship, my first 10 years of my career at Mayo Clinic, and I can confidently say now, two days after Strategic Coach, that I am an entrepreneur with a specialty in curing congenital heart disease.
 
Steve Krein: I'm so glad we had that recorded, because for you to say that, so both emphatically, but I have that realization as one of those breakthrough moments that changes the trajectory of your life. That's great.
 
Dan Sullivan: Yeah.
 
Steve Krein: We have so many questions, but we're not recording the podcast yet, are we now?
 
Dan Sullivan: Yeah, we're on. We've been on for-
 
Steve Krein: Oh.
 
Dan Sullivan: Oh yeah, yeah.
 
Steve Krein: Oh great. No, fantastic.
 
Dan Sullivan: I never leave the green room out of the podcast. The thing that captured me right away, and I think Tim and I kind of hit a note very, very quickly after we met on the trip. The thing was, I got a sense right off the bat. I said, "You're not just creating a cure in a particular branch of medicine. It seems to me that you're creating a model for a new, entirely new approach to medicine, period." He's got a very interesting model that I think we should start off with, but talk about the problem first because the congenital heart disease, up until now, it's been pharmaceutical Band-Aids basically that they've been using mainly to deal with something that they just had no other solution to.
 
So can you talk about kind of the tragedy, because it's one of the more tragic of diseases because it's already detectable at the fetal stage. And can you just talk about... Because a lot of people just don't realize, one, is the frequency of it, but the other thing they don't understand is just the hardship aspect for the individual. I mean the baby in the making, and then also the parents, and I think also the medical practitioners who are working with this, it's tragic for them.
 
Tim Nelson: So let me start by telling a story, Dan. You may have heard me share this story before, but it's really when I first experienced the tragedy of congenital heart disease as a person. I was in medical school training to be a cardiothoracic surgeon. I was doing my PhD in developmental biology. I spent every extra minute I had in the cardiac OR for many years, three, four years. And I got to know some amazing clinicians, surgeons at the Children's Hospital of Wisconsin in Milwaukee, Wisconsin. And I developed a trust and rapport with them, and I was in the OR with them frequently. And there was a week that I remember, and I remember because I feel guilty. To this day, I feel guilty about this story. We were doing a surgery on a very small child that required a Norwood operation, a few days old, had less than 50% chance of surviving the surgery, but there was 0% survival without the surgery.
 
So you had to do it. Long, long procedure, extremely talented team, and we get the child out of the OR doing well. And I literally remember high fiving each other, walking out of the OR, that we were part of a team that just accomplished an amazing feat. And as a medical student, is there anything more intoxicating, addicting, or motivating than being part of an experience like that? But quickly, within days, I was in the clinic seeing a four-year-old child that had had the surgery four years earlier, had three or four multiple surgeries after that. And we now were telling this child's family that there was nothing we could do for this child. That the heart was failing, they had high antibodies, they weren't a transplant candidate. And you looked in the eyes of the mother when you now are sharing the news that there's nothing else we can do.
 
And that made me feel incredibly guilty about two days earlier when we were celebrating. Celebrating what? Celebrating four years of extending the life of a child. That's something to celebrate, no doubt. But that's not what we were celebrating at the time. We were celebrating that we cured this child. Little did we realize that we really were just delaying a more painful conversation because we're not fundamentally curing anything, we're palliating it. Boy, that didn't sit well with me. That bothered me for a long, long time. And as I tell the story today, it bothers me that I had that feeling. But I'm grateful for that learning if at the same time. So what is the reality with congenital heart disease, that one in a hundred children are born with some form of congenital heart disease, one in a hundred. That's pretty rare, but also not very rare, depending on your perspective. These kids in the most severe forms will have to have multiple surgeries and will not have more than a 50% survival till their fifth birthday.
 
So 50% survival to their fifth birthday is a reality of the best care in the world. And that's so bad that there's many first-world countries that don't even offer these surgeries for these kids. They recommend and demand comfort care. That's the reality as we sit here today and talk about this in 2022. So it's tragic. It's life and death of a child. It's it nobody's fault for this. It's not mother's or dad's fault that they get into these situations. It's stochastic of who finds themselves facing this reality. And there's not a large enough market for the large company's investor, VC Community, to put money behind it because it's too rare. There's bigger opportunities for larger investments. So this is the reason pediatric cardiologists and pediatric cardiac surgeons have a chip on their shoulder because they feel like they're neglected. They feel like nobody's listening. They feel like nobody cares about these children and the fact that there's not money for devices and therapies.
 
Well, complaining is not very motivating to an entrepreneur, right? Complaining is the start of where the solution is. And so we fortuitously lucked out and got to meet some extraordinary people early on in my career, specifically Todd and Karen Wanek, who are the owners of Ashley Furniture. And they are personally affected with their daughter, Gabrielle, who has this condition. And they said, "We want to change this. We want to do our part to change this." And we formed a partnership at Mayo Clinic in 2010, and we've been on a mission to leverage the philanthropic community to focus on the rare diseases that are neglected and build focus programs that can be sustainable and scalable. And so the rareness of congenital heart disease is probably the greatest gift that we have had in our journey thus far.
 
Dan Sullivan: The thing that I find very, very interesting is the one donor model that you created where you have a no-exit strategy. So in other words, the donors here, the parents, they said, "We're not going to start this research and at a certain point say, 'It's not doing what we wanted to do; therefore, we'll do something else with the research.'" So they had an agreement up front and all through that there was no exit to the particular objective of their money and your skill.
 
Tim Nelson: Yeah, no, that's right. I think that that's a critical-
 
Dan Sullivan: Steve, you have many, many stories with your broad spectrum of different passions, different donors, different medical practitioners, but I think this rings true.
 
Steve Krein: Well, you hit on something, Tim, that is the key to all of the innovation in healthcare to really see it all the way through, which is starting with impact aligned partners. There has historically been, for the most part, a reliance on either retail investors when you take a biotech company public and you kind of use the public markets to fund it. There's basically a black and white, yes or no, did it work or did it not work? So it's kind of a little bit of a lottery ticket. But then you've got venture capital and private equity, and regardless of what anybody says, 99.999% of them are financial driven with what they're really looking to do. And so if financially it doesn't work at some point, you pull the plug.
 
By starting with this family who cares deeply, personally about what you're working on, it's not about the financial return, it's about the impact that you're making. And therein lies step number one: finding a champion that's stepping up, who cares at all costs, by the way, to the end game you're going for. So I not only applaud you, but it's really amazing how you, I don't want to say stumbled on it, but you were able to fortuitously come together with this family. And so I wanted to ask that question first. How did you meet them, and how did you connect in with getting them to not only get behind it, but give you the full confidence that they're behind you?
 
Tim Nelson: Yeah. So Todd and Karen are remarkable people. Two of the most remarkable people that anybody on the planet could ever meet. I mean that with deep sincerity and authenticity. They recognize the position that they are in the world with what they've created with their private industry, and they recognize that they want to be part of a solution for something bigger. That's remarkable and there's many people out there like that, but there's not many like that with congenital heart connection. So they feel like they have a responsibility at some level to find the best team, build the best team. And they were at Mayo Clinic and they asked the questions, and I just happened to be a fellow at the time that had just made beating contracting tissue out of a mouse model and published a paper where we improved the heart function of a mouse.
 
And I was so naive at that time that when they asked, "What's next?" And I said, "Well, we did it in a mouse. Why can't we do this in a human?" I mean, as I look back at that, how naive I was, but at the same time, it's true. We did it in a mouse. Why can't we do it in a human? And they said, "Okay." Okay what? "Okay, let's build the team." And we had a five-year runway. And within that first five years, it took us two and a half years to launch the world's first clinical trial using cell-based therapies for congenital heart disease. And that was the progress that propelled the culture of our team forward that, why not do this in humans? We can spend our lifetime researching all the nuances of the academic insight to this, or we can push the imperfect thing forward and learn with the most important model system, which is humans.
 
And getting over that bridge into clinical trials has been the catalyst for all the progress that we've made thus far. And it gets us out of that academic mindset of "another paper, another grant" type of thing. And it keeps us into a product development focus. And that first two years was so informative for now what's going on 12 years of a journey that has grown to over 60 people, four INDs, and as we'll talk about, maybe the world's first approval for a transformative technology that we, the little red engine that could, is now leading the world with. So that culture of "why not?" is so, so powerful when you've got the right team at the right point of time.
 
Dan Sullivan: Yeah, and even at the, Tim, you were with us, Tim didn't speak till Sunday, but the trip started on Wednesday. And on the second day when we were in San Francisco, we went to the Gladstone Institute. And first of all, we met Dr. Yamanaka, which was kind of akin to meeting Einstein, a very self-effacing individual, very humorous. But in one of the other parts of the trip, we went into an actual lab where they had, might have been a mouse, and they had created the stem cell solution, and it was in a Petri dish, and it was related to muscle, I think. And it was really funny because it was just a Petri dish with a fluid, it was like a soup.
 
And all of a sudden, part of the surface of the soup went thump-thump, thump-thump, thump-thump. And then they said in 15 minutes, the whole dish will be going thump-thump, thump-thump. And you have to appreciate, it's really hard. There's no there's no brain there. It's the muscle itself. The intelligence is in the cells. So I'm sure you had that sort of sensation that I did. You know, you were probably an old hand at this, but I was sitting there and I said, "This is really quite extraordinary."
 
Tim Nelson: It never gets old to see those beating cardiomyocytes under the microscope. And that's what we did 12 years ago. And now we've scaled that to billions of cardiomyocytes and we have a manufacturing facility that's vertically integrated with this vision, and we are producing a quarter to half of your heart muscle from a piece of your skin. So from a piece of your skin, nine months later, we can put in the palm of your hand half of your heart mass of beating, contracting heart muscle tissue. And that's a miracle at some level, a decade ago, and now it's a commodity. And what we're doing is, we're bringing that forward to make a product that not only is focused on congenital heart disease, but will enable partners to scale this and make a self-sustaining, self-managing industry around this technology that will feed back resources to continue to be focused on congenital heart disease.
 
We will never lose our focus on congenital heart disease, and we will scale as partners and technology allows to grow this industry. But it all starts with the rare, the focus, and a philanthropic investor that can jump-start this. Because once it gets jump-started, it can take on a growth strategy that's not academic. And that's really the, we don't solve that, but that's the journey that we are aspiring to continue to build out.
 
Dan Sullivan: Okay. We've done the first thing you have to do when you create a mystery film. We've grabbed the audience, and the audience is now captured. So we're just going to say this is part one. And don't miss part two. Steve, just to wrap up our first podcast here. So Steve, just your sense because from a global standpoint and looking at many different disciplines here with many, many breakthroughs, what's your sense of the discovery story that Tim has told so far?
 
Steve Krein: Well, what I think, first of all, it's an incredible story and it is a model that I think for entrepreneurs, and it's called innovators who aren't even yet entrepreneurs, is we were talking about before we started recording today, for innovators and entrepreneurs, the idea of understanding how to find partners from the very beginning who are impact aligned is literally the difference between success and failure. So this could have been a very different 12-year period, not only for you, but for the people that you're impacting had it not started from the very beginning with—what you hear about in Strategic Coach a lot is "batteries included"—energy providing, impact-aligned partners who are supportive of what you're doing, hard stop. I don't want to run past that point because that is what so many people, whether they are research in the lab, whether they're entrepreneurs with ideas, whether they're doctors who want to start something, they fail to see how critical just the relationships you wrap around you are, and I know it wasn't luck, it was serendipity that brought you together with Todd and Karen.
 
And by the way, they'll feel the same way as well. You came to them, they came to you at a perfect time, but had that not happened, right, we might, A, not be sitting here. They might not have the feeling and the progress they've had. And so step one, and by the way, I love the science, but I'm going back up one level to say, how'd you even get here? The idea that you found partners who are the right fit is such a critical part of the picture. And the reason I'm emphasizing this is because I know you appreciate them and appreciate it, but when people listen to this, it sounds like, oh yeah, they're focusing on your innovation, but you had support and you had support from impact-aligned, patient people who weren't just looking for financial return. And I can't tell you how often entrepreneurs come in, they got a bunch of money raised, or they found a VC or they found angels who are just quickly talking about financial return.
 
You're 12 years in, and you're just getting to and through clinical trials and at the, I think beginning of what your journey's about. Twelve years in. So you need to have a 25-year or longer, if not lifetime, as you just mentioned, a mission and vision, and then find partners. So anyway, I just wanted to emphasize that as my- As incredible as everything is you're doing, I'm just enamored by the ability that you had to, 12 years long now, have a partnership that not only you speak so highly of but have had such progress with and how critical of a part of the ingredient that is.
 
Dan Sullivan: Yeah.