Dinakar Singh - A Father’s Call To Action - [Invest Like the Best, EP.428]

23:15We then started literally taking out full-page color ads in some of the political newspapers in Washington, Roll Call, Daily Hero, all that sort of stuff, so that all the staffers would see this very striking roll-color ad every day on this stuff. lots of stuff like that to really go and essentially create a real sense of momentum on the side. Because it did occur to us that while at the end of the day, development of the drug matter and getting companies involved would matter, everyone would move faster if they thought that the other guy was there too. And with the FDA as an example, that really helped.

23:46They worked with us and we said, look, guys, we need this to move fast. And so what can we do? And by the way, kids are dying. We can't afford to run a placebo trial if it doesn't make any sense. And so we worked with them and got their approval to essentially run a natural history study, meaning while the drugs were being developed, we basically paid for people's care for a handful of years so that we could have a log of what the natural progression of the disease was and use that as our placebo. And so when it came time for the trials, the trials didn't have to be placebo-blind trials, essentially because the FDA was willing to accept the fact that they'll compare the results in the trial to what were the natural history study results of kids normally with SMA.

24:24That saved a lot of lives and a lot of money because otherwise half the kids would have died in those trials, including potentially our daughter. With all the persistence and with a few little help from our friends as well, the first estimated drug, I think, was then and maybe still now the fastest approval by the FDA ever in history of any drug. Wow. Which is pretty cool. The good news, bad news, of course. My daughter ended up being on the first drug since she was 12, so has been stable since then, and has ended up being just the rock star of the family. went to Yale, won three of the 11 awards for most outstanding student, class speaker, you name it.

24:59And during COVID, amazingly, went on Hinge and met up with this unbelievably amazing 64 fantastic Princeton kid. They fell in love and they got married last fall. She's now getting her PhD at Cornell. So I guess we'll end up with our doctor in the family. But just watching her thrive has been remarkable. That said, the clock was the clock. Every year she got weaker until the drugs came along. In SMA, the progression typically would be kids get weaker, stuff starts falling apart, like your spine, and you need spinal fusions. And that means your spine is constricted. You can't grow. That creates lung damage.

25:36And then you start getting pneumonia and all sorts of stuff. And so you end up, I mean, in the old days, you have enormous deformities with children. And like many degenerate diseases, ALS, Parkinson's, even Alzheimer's, no one dies of SMA. it just makes you really weak and then something gets you, whether it's a cessation or it's choking or it's pneumonia more often than not. Val Kilmer is just a stray of pneumonia, but pneumonia was really just a side effect of throat cancer. In her case, our goal was to manically keep her strong as possible until the drugs can come along. And so physical therapists coming to see her every day, We built a pool in our apartment building for her because you need warm water and it's a special therapy pool.

26:24But that was important because when you're a person who's weak, part of the problem is it's circular. You're weak, you can't exercise and stretch your muscles and bones, so they keep getting weaker and weaker on top of the original poem in the first place. And that creates this devastating cycle. And so here, between diet, between exercise, between therapy, the goal was to go and keep her as strong as possible to hold off that damage from all these things. And it worked and it didn't work. She did end up eating spinal fusion and having rods put in her back, et cetera. But fortunately, those were late enough that she had already grown and so didn't create the deformity you normally see in someone else.

26:59She had problems with her hips that blew out and things like that. When she was turning 10, 11, every year, there became a major surgery. And even aside from those medias surgeries, she was in the operating room or she was in the hospital probably three times a year with severe pneumonia at risk of dying each time. And with all these things, it is a bit Humpty Dumpty-like. Once it breaks, you can't just put it back together again. On one hand, if it had been a year earlier, that would have been all the better. But the good news is that compared to what we expected at the onset, to see her here in a rock star and truly happy with amazing friends and husband is just...

27:35So touching. I describe to people, if you have a boat and you have a hole in it, trying to bale water out of the boat is not really going to be a useful strategy. You're going to sink just maybe a tiny bit slower. Once you fix that hole, and now there's water in the boat, now baleing water in the boat could actually be a really good strategy. Mission stage two now is that we're working on a ton of drugs that we think can regenerate muscle. Nerve is harder to do, but muscle is a little bit easier. and also help existing nerves get a little bit stronger on stuff. We have one already in the clinic.

28:07It's not the best one, but we expect to have three or four things coming forward that could be really impactful. And what's actually pretty cool about this is that the SMA drugs are SMA-specific. 20 ,000 kids, so it's a lot of people, but they're SMA-specific. These regeneration drugs will actually help lots of people. And it's ironic because SMA is actually becoming a poster child for this because cake muscle is an example. I assume that there'd be tons of people and experts that knew all about muscle development from muscle stem cells called satellite cells into muscles, et cetera. There may be six people in this country that know what they're talking about when it comes to muscle.

28:41It's crazy. I assume, well, gosh, if you've got A-Rod and steroids and all that kind of stuff, I mean, there must be big money in it. But the reality is muscle has been a really tough field for a couple of interesting reasons. There are two types of people that have muscle problems. People with degenerative diseases like SMA, muscular dystrophy, et cetera. or on the other side, old, weak people. Old, weak people are a disaster to go and do trials on. And you're trying to see what a moderate impact to make when there's such decline happening. And so clinical trials, and this is the problem with Alzheimer's, are very, very challenging in elderly-generating parents.

29:16And in that first category, people with muscular disease, until SMA, none of them had been solved. And so it's a bit like that boat that you haven't fixed the hole in in the first place. SMA is now becoming this really fascinating area because suddenly if you have an idea for a muscle drug, you can actually test an SMA and actually see whether it actually does something because now you've fixed that boat, if you will. And so it is funny, quite a difference from 20 years ago when no one cared. Now suddenly we're calling up people saying, look, we think there's an idea. Your drug can really work here.

29:46Let's go test it out. They're doing it. So fingers crossed. I think my hope here is that we'll end up with a handful of drugs in the next handful of years that could really help bring back some strength for kids with SMA and other things as well. That would be amazing because as amazing life as a daughter has now, she is still fragile. And when you're fragile, as you get older, things happen. And so if we can bring back some strength, that will be even more transformative and even more impactful. So it's exciting stuff. The third time I'll say it, one of the most remarkable, inspiring, incredible stories I've ever heard of this type.

30:19And I'd love just to put a bow on it by asking what the prognosis is now for a new child born with this issue with these drugs available from a very early age versus from the age of 12 when your daughter started on them? So a child born and getting the drug close diagnosis will never show symptoms. Unbelievable. 20 ,000 kids. Yeah. 20 ,000 kids and their families. Many of the people that we've gotten to know the best over the years are people whose kids are affected by disease because there's a commonality and it's devastating for everyone. Parents who lose their jobs because they keep taking time off and they They can't afford the insurance.

30:57I mean, it's just this horrible spiral. There was a family. The father worked at Walmart. They had twins with SNA. And he just wanted to cry hearing their story. That is the funny irony with all this stuff. My parents were both scientists, and they would joke that it was such a tragedy that both their kids became partners at Goldman Sachs. In some ways, this all came in a difficult circle because having some of the science background, but having the good fortune and the good luck and privilege of working and investing in finance helped us go and actually put that science to work. Further, amazing irony, Columbia was our leading center in all this, and my mom had worked on faculty at Columbia.

31:37And Roche makes the drug that my daughter's on, and my father got her job at Roche as a Roche scholarship that paid for my college. Unbelievable. Funny how it's ended up being a circular process, but it costs a lot of money. I think we spent probably$150 million of our own money on this. But in the scheme of things, the commitment that we made at the beginning to ourselves was that if there was a way, we were going to find it. And no matter what, make sure that we were able to go and drive through it. And winding back to where we started in some of this, I guess that's a bit of a stubbornness, but also maybe preferable word, it's the termination I saw in my parents.

32:17So in that sense, I think really, nothing less than one that I would do for my daughter. When I step back, I've now had the luck to hear the story twice. When you told it to me the first time, it seems almost absurd. If you submitted a screenplay for this, you'd get laughed out of the room by the producer. You're going to start one of the fastest growing investment firms, one of the most successful investment firms, save your daughter, save 20 ,000 kids, develop a drug, which just economically is very valuable to say, which is a footnote compared to the impact it has on the lives and the families.

32:50It's almost not believable. It's so incredible. It's such an incredible story. What you didn't say the first time, which makes it even more magical is the tie back to your parents and their persistence. And honestly, it's just one of the most incredible inspirational stories I've heard. And a follow-up question that I have is what you learned, maybe that you've taught other parents about persisting through years of this kind of effort and what advice you might give to people that have to dig deep every day for so long to be able to accomplish the thing that they're trying to do for a loved one or for a similarly powerful reason.

33:32Because it's not hard for me to imagine the love for the child, but it's hard for me to imagine the ability with my body to get through it for so long. And I'm curious how you did that? I think there's like two or three, we're getting into nursery school. And by the way, another saga and another crusade that I'm going to be on more aggressively going forward, you know, the getting schools to care or take her was unbelievably hard. When she was going to private school, I think she was the only kid in a major New York City private school in a wheelchair. And I kind of know this as well, because I'm on lots of boards, public library, lots of discussion boards, lots of influential friends, lots of charity relationships.

34:14I couldn't find a single school that would take her. Many are perfectly accessible, but I'd get calls from friends on the board saying, let's take her, it's just not going to happen. The ostensible reason, I think, one school said she wasn't bright enough, crazy. Turned out to be maybe not bright enough for them, but bright enough to be straight as at Yale, super-colding and all that kind of stuff. They didn't know what to make of it. We had one school actually asked to see her medical records and talk to her doctor. before you consider. I mean, guys, you know, that's absolutely fucking illegal, Hans, but you had to do it because it might be illegal, but unless I tried, I mean, so when she would start in school, we would send up write-ups to other parents basically saying, here's what SMA is, here's what to make of it.

34:56But in any event, for nursery school, she went to All Souls, which is the Ontario Inchurched School. And initially they didn't want to take her and they said, look, there's a great cerebral palsy school you can send her to. I'm like, yeah, that'd be great except she doesn't have cerebral palsy, guys. This is a totally different disease. But eventually, I think they felt badly and they took her and she had a great experience. But you're supposed to go and volunteer to give sermons as members of the congregation. And so I did. I'll read you that quickly. Speak to it again. Please. Most of you probably never have listened to me.

35:24We certainly hadn't. And we're horrified by what you learned. It's the most common genetic killer of infants and it's untreatable, incurable, and eventually fatal. It's described as a children's version of ALS or a genetic version of polio. Simply put, motor neurons die, muscles break down, leading to eventually fatal complications. In most cases, SMA killed in the first two years of life, in less severe cases, such as our daughters. Depression can take many years, so as the mind grows, the body steadily weakens and eventually betrays it. Obviously, we were devastated and shattered. And over the past year, our hearts have broken every day as we've watched her become irresistibly adorable and learn to sing, tell jokes, talk endlessly, but also lose the ability to stand up, the ability to crawl, let alone walk.

36:07the ability to even sit up by herself. And yet, three realizations have helped us slowly face the future. First, we've truly learned and appreciated the importance of friends and community. The comfort and love of friends has been a source of incredible strength for us. And meeting other parents with issues and learning from them, and the incredible challenge that many of them deal with, has been an incredible source of inspiration for us. We've realized that there are no good diseases, but there are many, many strong people, and their courage is truly infectious. far more than they need to cease.

36:39More than ever, we've come to realize how much deeper our reserves of strength are as part of community than as individuals. Second, through the strength, comfort, inspiration of our friends, we've gained some perspective and been able to focus on finding the joy in the life that we have. We slowly realized that if we just hold our heads in our hands, we're accomplishing nothing, for our daughter or ourselves, for that matter. And at first, it's hard not to be consumed by the shattered dreams and lost notions of what could have been. Yet over time, we've come to focus on the many good things that can be and realize that there is joy in every day.

37:16If anything, we're now much more focused on appreciating the little things in life. And today, despite all the issues, our daughter is as happy and joyful as any child we know. And we are as lucky as any parent we know to have a child as sweet and adorable as she is. So we've learned from our daughter. That while the sources of joy and happiness might be different than what previously imagined, that doesn't mean that the magnitude of the joy is any less. And third, we realized the importance of channeling the nettle anger and sorrow into productive channels, so as to perhaps have some good, some purpose, some meaning in all this.

37:51And so we joined with other parents of children of SMA in efforts to improve care and further research, that this disease may one day be eradicated. In doing so, we found a productive outlet for our sorrow and our anger, and also a real reason for hope. And finally, let me just say how grateful we've been to be part of such a wonderful community. The strength and comfort offered by many of you has helped us focus on life, not on sorrow. After all, in life, there are no do-overs, no retractions, there are no appeals. You either find joy in the life you have, or live a life without joy. And while the circumstances of your life might not be up to you, whether you choose to find joy and purpose in them is very much ultimately up to you.

38:37So that was the speech. Wow, Jesus. But I think it captures the process that one goes through. I think for every parent, it's part sorrow and it's part rage. And depending on the moment, sometimes it's more rage than sorrow. You just want to go and break everything. But I do think that you do eventually figure out that that is, well, very consuming. It's not going to get you very far under any circumstance. And so this is where knowing other people and talking to people that have gone through things like this actually is hugely helpful because it just helps you recognize that there's a journey on all this stuff.

39:10And so I think every parent I know whose child has an issue was unbelievably emotionally supportive to us. And as well, almost every couple of weeks, I'll get a call from someone saying, look, I've got a friend or someone, et cetera, who has a disease. They want to make an impact on it. They've heard your story. Can you help? And that's, to me, the greatest joy I have, speaking to other parents and helping them think about what they can do, what can be done, what can't be done, et cetera. I joined the board of Jackson Labs. They essentially invented mouse models and are still the leader of that.

39:40It's an incredible institution. No drug has ever been developed without using their mice. So I joke it's the most important biotech institute that no one has heard of. Early on, we had gone to them to work on building mouse models and making free so people could call them up and then send them ice over all. But I'm working with them at setting up actually a Rear's Use Institute. We're going to have a squad of people to do a bit of what we did in SMA because I hear all these heartbreaking stories and they're the same things that I had 20 years ago. People that want to make a difference don't just want to go and make random donations that they think will just be like throwing water on sand.

40:10They don't know how. In our case, we had a lot of resources and a lot of connections and money and could essentially go and reinvent or invent the wheel. But for other people, it's a waste of money. It's a waste of time, both of which are incredibly scarce when you're a parent with a child who's suffering. And so our goaliers actually have, they call it the ghostbusters of rare disease, where if you have a disease, you call us and we'll actually get some scientists to work on it to go and help you put together a plan. Not caring whether it's with us or not, but essentially help be the brain trust for people to want to go and think about game plans for trying to solve a disease that affects some of the care of them.

40:43How do you hope the world of biotech evolves or changes, given your incredible ground level experience, not only just knowing how the system works, and also the extreme steps it took for you to speed up timelines, but also knowing the potential impact can be so massive, 20 ,000 kids, no evidence, no symptoms in their life because of your work and everyone that you worked with and their work. How do you hope with all that experience and knowledge that the system itself evolves? Well, some good things and some bad things, I guess, that have happened leading to what I hope will happen next. On the good side, you don't have to bash someone over the head to get them to understand that emergencies can be lucrative for them.

41:27I mean, SMA has been, there haven't been that many, but when people have seen the money that's sort of been made on this stuff, people care. But the challenge remains, which is that if you're a company working on oncology, even if there isn't a drug tomorrow, you're going to be working on oncology for the next hundred years, and that information can be useful in other things. The challenge with ERGIS remains that a lot of these are pretty bespoke. So the difference from 20 years ago is that you don't need to convince someone that it can eventually be very profitable, but you still have to convince them that there's a good chance that they'll be able to go and cure it because that early stage investment is tricky.

42:00There needs to be a much more thoughtful effort working with NIH, FDA, and disease groups to find ways to go and have a much more thoughtful, practical early stage because scientists writing papers and grants is really not a very effective way to get this done. And there's still too big a gap between a good scientific idea and when a biotech company is actually going to go and spend the money and do it. You don't have to get it through the 10-yard line anymore, but you still have to go to the midfield. And so I think more novel structures would actually be great. And I actually took back to that NIH translational research program from way back when.

42:34While it didn't end up making that much of a difference in SMA because we just ended up throwing the money out and going at ourselves, it's a pretty cool idea. And if one could do that, again, it's that Ghostbusters idea that I'm doing at Jackson Labs. Because the problem is we found in this world that companies mean well, but they're not trying to solve a disease. They're trying to attach value to an IP that they have. Meaning, if you solve SMA with something that they don't have IP on, it isn't very useful. Scientists are in the business of getting grants, and you don't get grants for, let's say, parallel processing or rolling things out.

43:06You don't get a grant by saying, I don't think this is going to work, but I just want to prove it doesn't work so I can then move on. That doesn't get you grant money on stuff. But a lot of those things and the tools and things like that are very much the nitty gritty that actually get you through that early stage where you say, whoa, I've got something. And so whether it's places like Jax Labs, whether it's NIH, having these amped up translation research efforts where people can set aside a little bit of money, because honestly, that early stage doesn't cost that much either. It's later on that you really start going down money rabbit holes.

43:37But for a relatively small amount of money, you could actually go and get people a good chunk down the field to where companies would care more. When you think about, obviously, the flavor of the day is tear government down. Government did a pretty good job in some of this stuff. But certainly, we can make government smarter. And I I think whether it's government or whether it's institutions like JAX, there is a role here to be played that could be pretty thoughtful where a few diseases are picked at a time and a modest amount of money is put in or coordinated so that you actually end up having a game plan.

44:04Because what a lot of people just need is a game plan as opposed to handing money out randomly. And also a third party that's viewed as being somewhat neutral because academics are great people, but man, they don't like collaborating that much. And companies really don't like collaborating with each other because it's an IP problem. And universities actually now are having more difficulty collaborating because universities want IP because they've seen the money you can get from royalties and stuff like that. So having a third party that's sort of Switzerland and can be a bit of an honest broker on this stuff is actually pretty important.

44:35So that's my hope, finding a way to have a more thoughtful process so that people don't have to go and try and figure out how to go and see if there's something there. Now, on the back end, boy, I mean, it's good that people give her her disease, but the cost of this stuff is insane. I mean, what companies are charging is just nuts. I wish when we had put all the money in, we had put in restrictions on what companies could eventually charge, because a million to two million bucks a year is bonkers. I'll give you a funny example of it. I remember talking to the people of Columbia when the first drug was coming out, and it actually was a working capital problem that had to bring their CFO in.

45:13because since Columbia was a major centrist, you could fill in Harvard or Stanford or whatever as well, the SMA drug cost$800 ,000 a year the first one. And so to go and actually buy the doses to treat the kids would have cost tens of millions of dollars that they didn't have their budget. It's crazy. It's a real issue. And I still get calls, and we get calls all the time from people in other countries because, for example, there's a Goldman Sachs analyst who is from Uzbekistan, and they called asking for help because their family knows someone close to them whose daughter is diagnosed. And if they get treatment, they'll be saved.

45:51But Uzbekistan, there's no place to get treated in Uzbekistan. You can't just come to the US and get treated because all sorts of legal and other issues and loopholes. And of course, then you've got to cough up the money to do it as well, cost you a couple million bucks. You can't just go to London and do it because again, the whole regulatory framework is crazy. And so there are still kids dying of SMA. Even in cases, in this case, for example, the family had gone around through supermarket stuff, meaning cans and signs in town, raised$400 ,000 to get her treated. And they couldn't find someone to take the money or find a practical later treat her on stuff and show she was going to die or suffer unnecessarily because of crazy regulatory bureaucratic stuff between countries.

46:32We've got to figure out something on the cost. And maybe it's with these drugs, having some amount of money get set aside when there are these windfall profits to go and help charity care or things like that. But the notion that we develop these drugs and their kids that are dying because they can't afford them is pretty insane. It's hard for me to ask my traditional closing question in this particular case because of the story you've just told. And knowing that contained in the story is so much kindness in so many directions that I'm sure it'll be hard to know where to begin. But my question that I ask everybody is for the kindest thing that anyone's ever done for them.

47:09After my daughter is diagnosed, people just giving me hugs was about the best feeling on earth. And there's nothing more powerful than just compassion from friends, strangers, just to feel like you're all human together. I think in life, at our worst moments, just getting some of the people's strength and energy imbued in you a little bit gives you the ability to go and stand up and move forward the next time. I'm sure I speak for literally everyone listening when I say thank you for telling the story. You've imbued us, certainly me, with that same strength and determination. It's incredible what you've done already.

47:44I'm sure what you will continue to do. I love hearing about your daughter's current state and her wonderful marriage. And what a way to spend my day. Thank you so much for your time. Of course. Thanks, man. If you enjoyed this episode, visit joincolossus.com where you'll find every episode of this podcast complete with hand edited transcripts. You can also subscribe to Colossus Review, our quarterly print, digital, and private audio publication featuring in-depth profiles of the founders, investors, and companies that we admire most. Learn more at joincolossus.com slash subscribe.

48:31Thank you.