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The Tim Ferriss Show
#868: Tim’s Founder Kitchen — From Brainstorm to The President’s Office in Two Months (Featuring Jake Becraft, Strand Therapeutics)
02:15:12
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- [00:00]
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In genetic medicine, I would call it the Holy Grail. For the last 30 years has been thinking about how do we administer intravenous, which means into the bloodstream, genetic medicines that can get to places throughout the body. We've been trapped in one organ for the past 30 years and that's the liver. We are the first company that I'm aware of to show this extent of abscopal response in visceral deep organ metastases in a multitude of patients. And really right off the bat, what I want the world to understand is that we are standing right now on the precipice of a revolution in genetic medicine. We're going to be able to get to a point in the not too distant future where I think a lot of types of cancers are at the very least chronic diseases instead of death sentences.
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Hello, boys and girls, ladies and germs, this is Tim Ferriss. Welcome to another episode of the Tim Ferriss show where it's my job to deconstruct world class performers has been my job for more than a decade. This episode's going to be an experimental format. It's going to be half interview, half live jam session. Because many of the most fascinating conversations that I have I cannot record. They're often involving startup founders because for close to 20 years I've been an angel investor that started in 2008 in the Bay Area. And some of those companies include Shopify. I was the first advisor when they had something like 10 or 12 employees. Uber, pre Seed, Round Advisor. Then you got Facebook, now known as Meta, Twitter, Alibaba, Duolingo, Clear. It goes on and on and certainly plenty of fatalities. But when things are interesting, they are so interesting. And I've wanted to share some of these conversations, but when they're about fundraising or something really confidential, I can't do that. So I wanted to think up how I could create a series. In this case, we're calling it as a placeholder, Tim's Founder Kitchen. I'm sure there's a better name. Please let me know on X Ferriss if you have suggestions. But these are going to be actual brainstorming jam sessions with founders who are willing to share the audio. And in this case we have an episode with Jake Beecraft of Strand Therapeutics, which is one of the companies I am most excited about. They're very, very bold. And in this conversation you will hear an actual early stage brainstorming session that led two months later to those talking points being with the President of the United States in the Oval Office. So to speak. So you will get to track a position in conversation and a comms conversation and the homing in on that message that ultimately leads to hopefully some real high level policy change involving testifying in front of Congress and all sorts of stuff. So this is a rare instance where you get a before and after. And so it's a two part conversation with Jake. In the process of listening to this, you will also learn a lot about the future of medicine. You'll learn a lot about genetic medicine. And the whole thing, I think, is very, very exciting. Now, if you want to skip to part two where we kind of find our groo and you get to hear about the results of the earlier conversation, you can do that by hopping to about one hour and 18 minutes. But you will miss the early questions and the process of refining and refining and refining that ultimately led to those results. And to add one more note, on that initial dinner where Jake and I met in Boston, there were two other attendees. You have Jamie, who is CEO of Alden Scientific, A L D E N and then you have Phil, who is CEO of holobiome H O L O B. And both of them ended up winning ARPA H grants for the research and work that they're doing. And ARPA H for people who don't know, is modeled on the Defense Agency darpa, which is incredible in its own right. And ARPA H does not operate its own laboratories. Instead, it funds or empowers visionary teams to take bold, seemingly impossible challenges in human health. And they do that by pulling from private industry, universities and elsewhere. So this is for the high risk, high reward experiments and projects in biomedical and health breakthroughs. In any case, who is Jake in brief? But I won't spoil the party by giving you a polished description of Strand just yet. I will say Jake Beecraft is the CEO and co founder of Strand Therapeutics, a company building one of the most advanced programmable genetic medicine platforms in biotechnology. You can find him on X R sinbio, that's D R S Y N B I O and Strand. Be sure to check it out. Strand, as you would expect. S T R A n d t x.com, that's strandtx.com I really enjoyed this conversation. It's an experiment, so please, please let me know what you think. On X is probably the easiest way to do it. Tferriss T F E R R I S S and without further ado, that was a long preamble because I wanted to set the stage and I do really want your feedback. On this. How can I make this better? How can I make it more interesting? Let me know. But let's get to Jake Beecraft. At this altitude, I can run flat out for a half mile before my hands start shaking. Can I answer your personal question now?
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It is an appropriate time.
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What if I did the opposite? I'm a cybernetic organism, living tissue over a metal endoskeleton.
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Ferris show.
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Please bear with the first description. When we start off, that is the starting point. And Jake later gets all fired up, as I expected him to. And you'll see how we start kind of top of the funnel with something very broad, and it gets refined, refined, refined, refined. And then that leads into the second part where we get to talk about the results. What does Strand do?
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So Strand designs what we call next generation genetic medicines. You have DNA inside of your cells. That DNA makes RNA copies of itself, and then that RNA makes proteins. And actually life is all proteins. Your skin, your hair, your organs, every cell is basically just proteins stacked together. That is everything that we are, right? You don't really see the DNA and the rna, it's very small. The protein is what we think of as like our being. And so the way to actually intervene in disease, the way to get to its core, is to create the correct proteins. If you have a deficiency, everything from an enzyme problem to a rare disease to cystic fibrosis, it's usually a problem with a protein that is being incorrectly made by a cell. And so what we have figured out over decades and decades is what's gone wrong with that protein and what would need to go right to fix that protein or how you would replace that protein correctly. What we have not figured out is how to make the cells do that. And that's because it's actually a very complicated. It's a very complicated problem to tell certain cells in the body to do various different things. And so what we are really focused on building, we know what proteins need to be made, we know where they need to be made, we know what we need to do, is get the message of what type of protein to the place in your body where they need to be made. And we need to do that effectively and safely. And so what we have essentially figured out a way to do is take that message, which is in the form of a molecule called rna. A lot of people are familiar with it from the COVID vaccines, but those are very small examples of what RNA could actually be utilized to do. And then we have found a way to send those messages into the body into diseased areas where they can access the cells and essentially return the cells to a state of homeostasis, which either corrects the problem or in the case of cancer, removes the problem, any of those pieces. And so that's the base case of what we're trying to accomplish.
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Let me back up and give people a little context. So the first time we met was in Boston at a dinner. Do you want to describe? I don't think they'll mind. Who else was there? Who else was at the dinner?
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Another biotech CEO, Phil Strandwitz. And a. I don't know how to classify Jamie's job. He's a leading professor at the mit. Yeah, polymath. MIT Media Lab professor, healthcare entrepreneur, advisor to anyone who wants to know fancy things sort of guy.
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And then me, I'm already an investor in Holobiome, Phil's company. Love what Jamie's up to and very interested in what he's building as well. We can put that in the show notes. We'll put all that in the show notes. And then we met. And part of the reason I became very interested in Strand, there were a lot of reasons. So one is the technology, the results, the photograph, or I should say images that you showed me, which we'll get to in a second. Second is founder builder, who is technical, but for whom. Also this company. This is going to be a strongly worded statement, but is existential. You're not a hired gun CEO who has been brought in. This is very much entwined with your identity and personal mission, which I find very attractive. Quite interrelated with that is the fact that I found you to be a very good communicator over that dinner. I learned a lot. You recommended a number of books to me at the dinner. And then afterwards I'd say chief among which was the Genentech origin story, which is one of the best, I would say, business books I've ever read. Just unbelievably good because it also, and I can't believe it made it past all the Genentech censors, but actual contracts, I mean, screenshots of contracts, negotiations, mistakes, takes all of the serendipitous lucky moments and unforced errors by universities and so on that had to coalesce for Genentech to even survive. It's just an incredible story. And I also just, again, this is more for people listening than for you, but I'll continue to fluff a little longer, which is also that you seem to me to be very aggressive without being haphazard. You were just furious at this dinner when I started trying to get an idea of the general biotech scene in Boston and asking questions about various startups and figures and companies at how conservative and dogmatic maybe would be a very generous way to put it. You view a lot of folks, not all, but the default, the status quo. And in contrast, how you're going, you're taking big swings, right? You are taking big swings. So all of those things were attractive when it comes to Strand. Let's talk about the image for a second. What was the image that you showed me or images?
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I happened to show you a photo of one of our patients, one of the very first patients that entered our trial. The way that these early stage trials work in oncology, patient with stage four melanoma. In early stage trials, you end up with patients who have been through every, exhausted every option by the time they end up in your trial. And they often have pretty progressed disease. And so you hope you can offer something to these patients. They had melanoma, so that's a skin cancer. But they had not only aggressive, what we call cutaneous metastasis, which is across their surface of their body and the skin, but they had what's called visceral metastasis, which is, that's actually what kills you in melanoma, is the metastasis to the organs of your body. And it was in their lungs, it was in other sorts of areas, I think muscle deposits and bone deposits. And in addition to that, this patient had had multiple other therapies that melanoma responds very well to. What's unfortunate about the current state of affairs in melanoma and in some cancers is we have these immunotherapy drugs. The biggest blockbuster of the last few years is a drug called Keytruda from Merck, incredible miracle drug, won a Nobel Prize a few years ago in melanoma. If you respond to that drug, a lot of patients do, that's great. If you don't, the likelihood of survival begins to diminish very quickly. And this patient had had Keytruda. They had had a whole number of other drugs through many what they call lines of therapy. You get a drug, your cancer responds or it doesn't. If it doesn't respond, you go to the next and the doctor, the oncologist cycles you. And this patient was at a fairly advanced hospital that not only had given them what they call the standard of care and then the second line standard of care, they had given them actually a number of other. Just like maybe this will work, maybe this will work. You know, you're trying to help the patient stay alive. And the picture that we have and this is in, you know, if someone, if you Google our ASCO poster, which is a big clinical oncology conference.
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How do you spell asco?
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A S, C, O. It's an abbreviation for the American Society of Clinical Oncology. It's a meeting every summer in Chicago that sort of is the big breakthroughs in clinical medicine for oncology. It's the top of the top in a lot of ways for people. Big results, small results. We had presented this photo there and I had met you a little bit afterwards to show the photo itself is quite striking. And it's in that poster.
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Yeah, it's basically a body riddled with cancers. They're everywhere.
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I like to say you don't have to be an oncologist to look at that scan and understand the extent of which this patient responded. Sort of just riddled and then no more. And one of the things, as a scientist. Right. Tim, you mentioned something earlier which was this is more than a company for me. And actually a company is only about one third to one half of the time that I've spent on this mission to make genetic medicine work correctly for patients. One of the greatest accomplishments in that career that I've had thus far is being able to say that you did help a person. If that was just one person, one patient, I'd say, wow, what a career we dream of. More, we have big ambitions here at Strand. I have ambitions for how many people in the scale at which we're going to be able to help people. However, that was the first time that I really felt like our science went out into the world and it took someone's grandmother and not only kept them alive, but we're a year and a half in and they still have no detectable lesions.
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Yeah, it's wild. In the investor deck, the pitch deck that I initially read and had, I apologize for that. But like a million and 500,000 questions about what? For the non technical folks, the Muggles, they can look things up and are curious. What are things that stuck for them, like particular slides or phrases? Certainly the images. But is there anything else that comes to mind that really resonated with people from that deck?
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I think there's one other bigger generalist investor who had come into the round personally and I had been having a conversation with them about something in oncology that we call the Kaplan Meier curve. Kaplan Meier curve, if you're looking at oncology results, is Sort of a survival graph. So you have, you know, you maybe look at like two years and you look at from 100% where you start the study, and then it looks like a step ladder going down. The standard of care line has some amount of, you know, people like steps down. And you want to have your drug be significantly above that. Either having more people alive longer or, you know, you have like a, what they call the long tail, where like everything goes to zero in standard of care at a certain time point. But you have an amount of patients that just like look cured. They continue on for many years. And in drug development, we get very used to looking at those graphs and sort of making very statistical calls and saying, oh, this doesn't look like it's active or this drug's or isn't that great? But I think one of the things that I've spoken to some generalists, some of our larger investors who maybe aren't from the biotech world, and I've tried to zero in on some of those survival graphs with, is to say, when we look at these steps, these are lives. The lines that go down on this, the vertical part of the step is someone's loved one dying, but the ones that go horizontal and every time you see something go further along, that is someone who got to experience, even if it's just three months, you have no idea what that means within that person's life. And when we take that Kaplan Meier curve and those steps and we zero in on each patient, we start to look at them and we start to say, like, this is a patient that didn't think they would see Christmas in 2024, and they just celebrated the new year of 2026. That I think is meaningful in what we're doing now, whether or not that will be a good product. The good drug is like, can someone take this? And it does sound like a good. Injecting a therapy into someone in a way that is very hard to replicate, but did a great thing for that individual person is a good drug. Fundamentally, it is a good drug. It helped that person. And a good product is much more. This is where the idea of how we get medicines to people come into play. I'll give you a different example. There's something else that we're working on called in vivo cell therapy. Essentially, there's an ENT type of science that we have discovered how to take the immune cells out of a patient, take their immune cells out, reprogram them so that they learn how to attack cancerous blood cells, and then Put them back into a patient. They are phenomenal drugs. There are people who are about to die of like myeloma and then they get this drug. But the drug costs, not making money. The drug costs $750,000 to make just to manufacture. It costs three months of time to manufacture. It's very hard to see a world in which that drug has a large impact on the patient population because of the fundamental costs. The cogs, the cost of goods sold. Not biotech, just straight business. The cost of doing it and the time it takes to get it to people, that's a bad product. And so if you could say, instead of taking the cells out of the body, if you could reprogram them while they're still in the patient, now you have a good product. If you can make the cells recognize the cancer, the immune cells program to activate against the cancer in the same way. But make it an outpatient procedure where a patient just gets hooked up to an IV bag for two hours and then goes home. That is a phenomenal product.
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I have to look at this from the perspective of a non specialist, because that's what I am. But if you were giving a TED talk on this and had to kind of get across at least part of what you're doing, I feel like what you just said sort of hits the nail on the head. Within the first few minutes, you'd have to talk about the central dogma, so to speak, of DNA as master copy, so to speak, MRNA and then protein. But just in brief, could you describe what the treatment actually looked like for the patient in those photographs, the before and after, like dots everywhere representing tumors. And then, holy shit. I think everyone, whether they're technical or not, that looks at that deck probably had the same response to those images.
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In cancer, you have chemotherapy, I think people are fairly familiar with. You also have immunotherapy, which is the ability to activate the immune system to attack the cancer directly. And that's what some of the biggest blockbuster drugs of all time are currently. Merck's Keytruda, Bristol Myers Squibs, Opdivo, and then there's a number of other types of immunotherapies which are classified as checkpoint blockades. So what that is is your cells essentially have a way to tell the immune system that they are your cells. So you don't want your immune system to attack your own body, obviously. And so one of the mechanisms that you have is this IMU signal that you can send to the immune system, your cells can send to the immune system. Cancers Hijack that mechanism to protect themselves from being attacked by the immune system. And what we figured out was a way to block those signals. And that's the entire field of immunotherapy. Not the entire field, but I would say a vast majority of the field of immunotherapy and the successes of the last decade of treating cancer and also commercial for a lot of these companies has been based on further refining better checkpoints. The problem with that is that they're all very similar mechanistically. And so if one doesn't work, if you have cancer and I give you keytruda and it doesn't work, the chances that the next types of therapies will work, since all of them are very similar mechanistically, the chances diminish quite drastically. And there's some nuance here. And I'm sure if there's oncologists listening to me, they're like, no, but you don't know. In double negative this cancer, if you combine with these, it doesn't matter, right? In general, these mechanisms become degenerative, and we don't have good additional options to excite the immune system. A second theory for going back to the 90s was if instead of just blocking the cancer's ability to hide from the immune system, if that's not enough, what we actually need to do is we need to activate the immune system directly. And it would be best if you could send that activation signal from the tumor itself. So now you have a tumor. Instead of just blocking the tumor's ability to hide, you, actually have a tumor that's sort of screaming like, I am a foreign object. Please come and eat me. That's kind of how immune systems kill things. They eat the other cells. And so the issue, this is not new. This is basic science from immunology from the 90s. The problem is we haven't had a good way to get the tumors to send those signals. We've tried to make the signals in the lab and then inject them into the tumors. And the problem is the signal just goes away immediately, and then it's circulating in the body, and the immune system doesn't know what's sending the signal. We've tried everything we can to make this signal artificial and it into the tumors. And every single time we do it, it's either not enough in terms of no efficacy, or it activates the immune system in all sorts of places we don't want it, and it causes all sorts of toxicities. And so what we are doing with our Medicine is delivering the instructions into the cancer cells in a way that causes the cancer to basically send its own signal out. So it's artificial in that we have made it in a lab, but instead of making the signal, we're a message that tricks the cancer into sending the signal. And so that is drastically different. It makes a huge difference in both safety and efficacy, because now you are recapitulating how the signal works naturally. If the cancers weren't cancerous, if they were just deregulated and cells were starting to grow out of control, your cell would naturally send the signal and be like, oh, no, something's wrong. And your body would take care of it. You actually generate cancer like, like all the time in your body in terms of dysregulated cells. Your immune system just comes in and takes care of it before it becomes like a, you know, when it becomes a real problem. That's when you get tumors. That's when you get the disease we call cancer. And so what we're doing is we're sort of resetting that system. We're having the tumors resend the signal out. And so what we created in that first drug was a very simple administration procedure. You take our genetic medicine and you inject it into the tumor directly. And what that is, the immune system comes into the tumor and it kills it. But then it gets activated by that killing process, and it learns what the tumors look like, and it can better identify the other tumors that have been hiding throughout the body.
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So it's something called the abscopal response or the abscopal effect, which means that one tumor is sort of what you've put the activating drug into. And that's where you know the immune system will attack first, but now the immune system is activated and educated to go and kill the other tumors. It's not new in the fact that like I didn't come up with that name. It has been observed in limited other settings of a few other drugs that people have gone out with. The problem has been that it's been very, very limited in terms of the abscopal response that other people have seen. So for instance, you would have a patient with a tumor, maybe melanoma patient, so they'd have a cutaneous lesion, a skin lesion on their chest, and then they'd have another one on their shoulder. And you would inject the one on the chest and the shoulder one would also kind of shrink. They're in the same region. The immune system is sort of like fighting the cancer in the same region. But you wouldn't necessarily see that happen in like the lungs. And so one of the big pushbacks on a drug like the one that we took to the clinic two years ago was you don't die from having tumors all over your skin. You die from when they metastasize into your lungs and into your liver and impact the organ functioning. Right? That's how patients die of melanoma. So if you are only able to address the tumors that you can either inject or that are near the injected tumors, you won't have an effective drug if a patient already is like, further along. We are, to my knowledge, one of the first companies, if not the first company to demonstrate a direct injectable drug into the tumor that in a large number of patients, this isn't a one off, it wasn't one miracle patient. That is a beautiful photo of that patient. And I'm so happy that they're still on the trial and still doing great. And it's amazing. But you know, this is about being broadly applicable because that's how you actually impact population level lives. And so, so we are the first company that I'm aware of to show this sort of like, extent of abscopal response in visceral deep organ metastases in a multitude of patients. And really right off the bat, I mean, this is from the very first patients we put on this trial, at the very beginning of it began responding. That is very uncommon. It's very uncommon to have patients on a phase one trial on the drug six months later. And of our first three patients that ever entered this trial in the summer of 2024, two of those three are still on the trial 18 months later. That is something that I think is fairly shocking. If we were a traditional biotech company, we'd be really happy with all of this data and we'd say, wow, let's take this forward. However, I think the real message of strand and what we can accomplish in genetic medicine Is we don't have to stop at just injecting into the tumors. There are a number of concerns with injecting tumors from a product perspective, not a drug perspective, but a product perspective. The difference between a drug is all about does this work and a product is about how will these patients get these drugs. And, and injecting directly into a tumor is doable and most oncologists can handle it, especially for skin cancer patients. But as you go to rural health communities, it gets harder and harder to have doctors that have that training. And as you get to other sorts of tumors beyond skin cancer patients, some of their skin lesions have been removed by a surgeon. And then you go beyond skin cancer. How are you going to inject a patient with non small cell lung cancer? Like you start to get this idea of there's a limited amount, amount of patients you can access, right? And so you have a product maybe limitation in cancer. The way that we actually treat cancer patients is that there's an infusion clinic. You go to the infusion clinic, the oncologist and the nurse practitioners, technicians hook you up to some sort of an infusion and then the oncologist can monitor multiple patients at a time. And that's what our infrastructure looks like right now of how we treat patients. And if you want to have the largest impact in medicine, you need to make medicines that plug into existing infrastructure. As much as you want to like tell everyone, hey, change everything about how you think about treating patients. The way to like have a near term impact is to build drug solutions that can plug into existing infrastructures. You know, if we become a giant biotechnology company that has all sorts of resources, maybe we can talk about changing how everyone gives drugs. But for right now, we do need to, if we want to be able to help the most amount of patients in the near term, we need to plug into that infrastructure. We need to find ways that we can access organs. I take in addition, the bloodstream is also a really good way to get around the body. Believe it or not, the bloodstream carries oxygen to everywhere in your body. And so if your drugs can travel through the bloodstream and get where they're going, very effective in genetic medicine, I would call it the holy grail. For the last 30 years has been thinking about how do we IV administer intravenous, which means into the bloodstream, administer genetic medicines that can get to places throughout the body. We've been trapped in one organ for the past 30 years and that's the liver. The liver naturally filters your blood and thus it picks up a lot of these genetic medicines that we put into the bloodstream. And so what we've done for the last 30 years is figure out how we can treat diseases in the liver with this old Internet meme, which is like, step one, blank. Step two, question mark, step three, profit, right? I remember, like the old days of Reddit, people used to use that structure, right? Step one, do this. Step two, question mark, step three, profit in biotech. In genetic medicine, the joke is like, step one, prove it works in the liver. Step two, question mark, step three, we'll treat all these diseases. And after 30 years, we've really nailed step one. And step two has remained this big question mark. And so when we started Strand, our number one goal actually was not even to get to this first drug. As amazing as it's been for these patients, and as happy as I am that we have been able to help those people in their lives, and as impressive as it is, our main goal was to solve this step two, question mark, that's been sitting there in plain sight. And I guess the bigger piece here is that everyone who thinks they know what they're talking about in genetic medicine will say, well, the issue is delivery. And it's like, you need to be able to deliver. And I'm like, that's a very hand wavy. Again, it's just a cheap answer, which is not wrong, but it is incomplete. And I believe that it's actually three problems at once. It's three children in their father's trench coat pretending to be an adult. It's like, we're delivery. And then you open it up and it's like, potency, specificity and delivery are all here inside. And no one wants to hear that because people want simple solutions. They want like, oh, it's delivery, so we'll just fix delivery. And just 30 years in, no one has a good idea about this piece. Right? And I'd say that the thing at Strand that, like, when I started the company, that I just could not understand why everyone didn't see what I was trying to tell them. And I was very bad at pitching. I was. You think I'm too much of a scientist now? Perhaps. Or maybe your audience does if they're listening. But, like, man, you should have seen my very technical, zero market insight pitch deck of 2018. That is complete dog shit. It is an awful. I can't believe someone funded us. I'm a huge fan of Elon Musk's first Principles Based thinking. Right. I don't know if Elon is the One who invented first principles based thinking. But I think he's probably the main evangelist and popularizer of this thinking modality where if you take SpaceX for example, his idea was what is the thing preventing commercial spaceflight? And it's dollars per kilogram of launch. It's just like dollars per kilogram. That's it. How do you get it down? And you start to like, well where's the cost centers in a launch? And you go, okay, well the cost center in a launch is in like these rockets, these launches that we're trashing 80% of it. And you go, well, why don't we just reuse them? And people are like, well they do this, they do that, they're hard to retrieve, they're in the ocean, they're floating and they can't. And he goes, he goes, what if they like land themselves? And it's like, that's an insane thing, that's an insane person thing to say. What I want the world to understand is that we are standing right now on the precipice of a revolution in genetic medicine. And that's important for a number of reasons. One, it's important because there are near term diseases that we're going to be able to solve. We're going to be able to get to a point in the not too distant future where I think a lot of types of cancers are at the very least chronic diseases instead of death sentences. We all want to get to cures, I want to get to cures. But we are getting at least to a point where it's a manageable disease that's I think a near term piece. But we're standing. There's sort of multiple lines of technology that are coming together that I think people are not fully appreciating what they're going to mean for the future of medicine. And so there's a lot of focus right now on AI based drug discovery discovery and people are building proteins and antibodies and all sorts of stuff with AI models that are doing incredible things. We have decades of work on designing exquisite proteins that do all sorts of stuff from edit genomes to cure whatever in some sort of mouse model. What we don't have is the infrastructure, the medical biomedicine infrastructure that gets any of these things, these discoveries, whether they're made by a human with Microsoft Word stitching amino acids together, whether they're made by an LLM that knows exactly all the pieces that are going to make this, whether it's made by high throughput screen of 14 different robots in Concert, it doesn't matter. What matters is how we're going to get those into patients, how we're going to get them into the places they need. And I think about this as this infrastructure of medicine comes forward and what this will actually mean for the future of healthcare. Anyone in any sort of a place of power throughout the world, I think needs to understand where in the next 10 to 20 years we very well may be headed with medicine, which is smaller indications, niche indications. We are moving in a way where I think medicine becomes maybe not completely bespoke, but much more refined. And the way that we get there, we're going to get there technologically and we're going to get there from a design perspective much quicker than we're going to have the infrastructure to actually deliver those medicines to people safely, effectively, at scale. And so our goal at Strand and our challenge is building drugs today that impact patients lives. We're not a research institute. Our goal is not to do really cool research on mice and join the ranks of people who have cured mice of cancer. There's millions of them. There could be a Nobel Prize every five minutes for someone who's cured a mouse of cancer. Our goal is to cure human beings of human being cancer. Our goal is to cure human beings of human being diseases and do so in a safe, effective, scalable way that impacts a person's life as little as possible. And that is what we're building. We're building as a commercial organization, we're building drugs today. But what we're doing is we're laying the groundwork for this infrastructure to where, when we're successful in tumors, with the new trial that we're running this year, when we're successful with being able to iv deliver infuse a genetic medicine that goes to the tumors, we have an instruction manual, what we call a payload, the protein that we're tricking the cancer into making. We have one that we've chosen. But success there actually means that I could now in six weeks design a completely new protein to be delivered to the tumors. And I could just go over and over and over again. I'm only going to be gated by the infrastructure. I have to build like new ones of those and the FDA's ability to move quickly with us as we try to test new and newer things. But we know the general high level safety of this that's coming, that's coming in a lot of other areas of the body where we're designing things to get into T cells so we can help temporarily influence the immune system so you could take out things like autoimmune disease and allow patients to, to revert back to their pre treated state without doing any sort of genetic modification. We're trying to get all sorts of these therapies forward and every time you have a success, we lay the groundwork for this infrastructure going forward. I want people to understand it. One, because we have large ambitions. A lot of people have thought first they thought that the first principle based approach we were taking was incorrect. They're like, it's a delivery problem. You need to build a better delivery vehicle. Why don't you focus on that? And I'm like, okay, everyone's done that now. We've shown this complex solution actually fixes this age old problem and we're going to be continuing to move that forward. I'd say the biotechnology industry will be dragged kicking and screaming into the future or it will be built up in a new way from new players for us. I want to find the people throughout the globe who want to partner on these things. The innovators in America. Those are all sorts of different sorts of folks.
- [41:43]
B
Let's dig into that just for a second. For instance, with this podcast, let's say I was like, well, I got good news and I got bad news. The bad news is I can't put this out to my whole audience. The good news is you get to tell me which thousand people I send it to and that gets hand delivered to 1,000 people. And I mean, a similar way to look at it would be like, all right, you're giving a TED Talk, but it never gets shared online. It is only for the thousand people in that room, but you get to hand pick them. Who are those people? It could be categories of person, but how would you think about that?
- [42:19]
A
I think policy leaders, not just in the United States, but across the globe that need to think critically around how we are going to both handle, enable and empower the future of medicine. Because things, incentives, things are going to look quite differently ten years from now than they do today in terms of the scope and the style in which we can build medicines.
- [42:43]
B
And the policy leaders are important because ultimately they're going to determine the rules by which healthcare is played. Is that one way to put it?
- [42:51]
A
Yeah. Healthcare is very similar to the space industry. And that policy leaders essentially have two major pieces is that they are both the arbiters of what is allowed to be done and they are a major payer, not the only payer, but they are a major payer of the purchasing of that. And so as the fundamentals of medical development change, now I'm not making a drug that I hope to give to 2 million people worldwide. I'm making 100,000 variants of a drug that I'm hoping to give to 10,000 people worldwide, or 10,000 variants of a drug that I hope to give to 100,000 people worldwide. And I get to more people, but there's more variants. Both the regulatory and the payment systems, I think, need to adapt themselves to allow for that. It's on us, the medical innovators and the engineers and the entrepreneurs to build systems that are still good products. You have to think about where you're going and then build a system that can still be a good product. If it costs 10,000 times as much, it's not going to work. It just won't work at scale and you won't access these patients. But if you can see a path forward and think creatively. And one of my. I'm not a politics guy, but I am fascinated by policy and how incentives shape the future of highly regulated industries like biomedicine, like space, like all these things. And that is regulation plus payment. I think that there's incredible work to be done and the last big time of, I think, productive collaboration between worldwide policymakers and the United States as a leader. But the last big collaboration of that came in the 80s when biotech started to take off. In the 90s, when it really ripped, when we started to harness the power of recombinant proteins. The Genzyme book, you plugged it earlier. That's phenomenal.
- [44:43]
B
Genentech.
- [44:44]
A
Yeah. Genzyme's the Genentech of Boston. I get the two of them were like, but the Genentech book, really studying the history of genzyme. Genzyme actually had the leader, Henry Tamir, who was the actual quarterback, I'd say, of the policy innovation, worked with government officials to figure out what will this new class of medicines look like that aren't just small molecules that you can take home. Now we have antibodies, we have all these drugs that are amazing because of it. We have the Orphan and Rare Disease act, which led to people building these rare diseases, diseases and so rare disease drugs. I'd say we need to have more productive collaborative conversations around what the future will look like, because things are going to change very fast. You know, I read the AI report from the White House, for instance, and the sort of how the state of AI is. And I looked at, I read through it and I was like, they actually need one of These for biotechnology as well, because things are changing as rapidly and it's going to be further accelerated by AI. And if we don't have some productive conversations, we're going to be stuck in one of two places. One is where only the ultra rich can get the really disruptive drugs because they're the ones who can pay for it. Because we don't have a system set up to have these new radical changes commercial quick enough or dispersed quick enough, or the second is the inability to pay, the inability to find ways that like support an ecosystem makes a uninvestable thesis for investors. And so all of these like great innovations that we have coming out of the lab right now just die on the bottom at their knees because. Because just like space, space industry, it's a long time cycle to read these things out and you need capital to get there.
- [46:22]
B
So a lot of what I try to do in my own meandering way is kind of answer the thousand people in a room question and then to figure out, it's like, okay, let's just say you're spending time in dc, you sit down, somebody, their staffer convinced them to sit down for 30 minutes. What do you lead with then that can inform potentially the website or appearances on podcasts and stuff. So just in case it's helpful, I can obviously share this afterwards too, but it's like a couple things come to mind and I think in terms of, so once you identify the people in the room, then it's like, what does the TED talk look like if you got 20 minutes on stage? And I mean, you're good at this stuff, but sometimes you're so close to it that it's helpful to have a muggle who's coming at it.
- [47:02]
A
No, I want to hear this, Tim, by the way, a free communication lesson from someone more versed in the area.
- [47:09]
B
Well, yeah, thank God, because I can't do science, so got to allocate responsibilities. Well, you don't want me in charge of developing immunotherapy. So the Christmas story and the photos. So if you kind of started with that, I'm just walking through in my made up TED talk. And then you talked about, let's just say you went from there like, okay, let me take a sidebar for a minute. And you talked about SpaceX and their reusable rockets. And the analogy also of once you have this engineering platform developed from first principles, now you have something that is payload agnostic. Once you've made it economically feasible and you have this platform, whether you're Launching superconductors into space as an alternative to propellants for a satellite reorientation. You should check out this company called Zeno. I might have to to redact this, but they're in New Zealand. C E N O. They're pretty fucking amazing. But whether it's that, whether it's something else is entirely up to you in terms of deliverables because you've done the hard work of developing this engineering platform then talking about okay well what does that actually mean for biotech? And you've got the holy Grail. How do you IV administer genetic medicine? And then you could segue to. Because there's a good drug and there are lots of good drugs that die. Why do they die? Because they're never going to actually make it it into production, so to speak, at scale in healthcare. And I've seen a lot of analogies with this and I won't digress too far but with psychedelic medicine and it's just like, okay, you need an overnight nurse. This is going to be an eight hour experience or six hour experience. And sure, you could argue that you might have the rich people pay $10,000 out of pocket and that subsidizes the, it's sort of like Uber Black subsidizing UberX. There is an application there. But if it's fundamentally incompatible with current healthcare, you're trying to win a race with your ankles tied together, it's probably not going to happen. And then you have people looking at 5 Meo DMT instead of Psilocybin stuff. And I have my own thoughts on that. But sure, it's like you look at the failure just real quick of MDMA assisted psychotherapy when it got in front of the FDA advisory committee, a lot of reasons for that. But then you have people coming out of the gate and they're like, oh, we tried to couple, they tried to couple psychotherapy with it. The FDA does not regulate psychotherapy. It became a huge quagmire of just confusion and therefore these other people are like, well let's do methylone. It has a much shorter half life. You can actually fit it into an hour, hypothetically. Right? You can decouple the therapy or just looking at drug effects and lo and behold it's making a ton more progress. But the point of saying all that is that you've got the kind of SpaceX you segue to the Holy Grail. And then what if you could reprogram cells in the body, what happens? And I do love the fired up hand wavy delivery thing. Because you're like, what they've missed is. And again I'm ad libbing here, so it might be an issue is that they're right and they're wrong. They're wrong because of reasons X, Y and Z. And this is a lot of hand wavy stuff. And we're still at a point where we're defining triple negative breast cancer by what it isn't. It's like if you have trouble with your shoulder and you're like, well good news, it's not elephantitis and it's not Parkinson's disease and you're like, how does that help me? It doesn't really. But then you say they are right about delivery in the sense that if you cannot plug this into healthcare and deliver it to end patients, game over. It doesn't matter how effective it is in an N of 1 or an N of 5 or whatever your small clinical is. These are not necessarily in the order. But talking about even though it's not the end goal, what if we could turn cancer into a chronic disease? It can be managed. And it's like back in fill in the blank, 1980 x HIV was a death sentence and no longer the case. Now you look on television and it's like you see ad after ad related to some preventative but also maintenance drugs that allow people to live with a chronic condition. So anyway, those are a few things that kind of hop to mind. I would be curious for policymakers, what are the things that most catch their attention whether from experience or hypothetically, what is it that actually gets their attention?
- [51:28]
A
I was in D.C. yesterday and my overarching message is sort of like there are two things we need to do better. We have to understand, we have to to build regulations that I think are common sense that still allow us to like more cheaply test drugs. Right now for a lot of reasons we have sort of vestigial, over many years reasons as to why we. It takes us a lot of money and a lot of time to just get to a simple answer on a medicine. Right? And that is creating a world in which the biotechnology industry is incentivized to do very small steps forward because the cost of failure is so high that you're trying to reduce your risk in a way that is let's make a drug that's 10% better. Because taking a truly innovative risk would be very difficult to underwrite for certain investors. I'd say at the other side, the thing that catches folks attention is to talk about how medicine is fundamentally changing and we all can See that AI is changing how business is done, how people build things, how people read things, how people parse through information. It's making highly motivated people 10x better, if not more. And it's not just AI and biomedicine. It's sort of multiple threads coming together of novel technologies of how we build medicines, genetic medicines and their sort of advancements, things like what we're bringing forward, our ability to diagnose diseases and subcategorize diseases and change the way in which we interpret how this disease is, the sequencing technologies which allow us to do that, and other sorts of computation and AI that plugs into those pieces, all of that's going to fundamentally change medicine. Because if I can't just make a decision around the drug that every breast cancer patient gets, and then I agree on the cost that that drug is, and I pay for it a number of years, and then the drug goes to generic and someone brings the next drug forward that's 25% better and blah, blah, blah, and we just continue along that. That's the non innovative way in which we've been developing medicines for the past number of years. And every once in a while we have a breakthrough. True policymakers tend to like that because it comes down to like numbers. And medicine is a very interesting piece in policy.
- [53:43]
B
What do they like? Could you just say that again? They like the idea of breakthrough versus incremental.
- [53:48]
A
They like trying to learn about it. When you start to talk about medicine, it's very interesting because you think about paying for medicine like the government or health insurer, but the government paying for medicine is a near term cost center that should long term reduce a larger cost center. So brand name medicines are 8% of US healthcare spending, but hospitals are 26%, something like that in the high 20s, I believe. And so you imagine that like for 8% of your dollar in health care spending, you are pulling down the amount of people that are now hospitalized, you are increasing people's life, you're keeping people in the workforce, you're keeping people in their homes, you're keeping people out of a system that no one wants to go to the hospital. And the government that pays for a lot of people's hospitalization in the form of Medicare and Medicaid doesn't want to pay for people to go to the hospital. And so you begin to talk about that, that system and you say preventative healthcare. But all medicine to a certain extent can be thought of as preventative if it's able to stave off hospitalization. It's at least, at the very least, hopefully preventing you from being in the hospital. And so policymakers like those conversations.
- [54:55]
B
I'm going to try to keep this from sounding too conspiracy theory, but what I'd love to know is what's in it for policymakers to help you? And that might sound strange, right? Because I'm not saying these are bad people and we could talk about the kind of industrial regulatory exchange programs another time, but that's a thing. So I guess what I'm wondering is how do you align incentives with policymakers so that they feel compelled and interested in being helpful? That's the big question that comes to mind. So let's just say there are a thousand policymakers listening right now, or if you're in the room. But what is your ask if they're like, hey, look again, good news, bad news. Bad news is I can't meet again. I'm just too busy. Good news is if you have a reasonable ask, I can greenlight it right now. But you need to do it. What is the ask?
- [55:48]
A
My first ask right now is we need to streamline how we test new medicines in humans in clinical trials. In fact, maybe if this ever sees the light of day, hopefully the A op ed that I wrote on like accelerating first in human trials and becoming a more innovative powerhouse as a country.
- [56:05]
B
Oh, where's that?
- [56:06]
A
I just wrote it a couple weeks ago and we submitted it to a handful of places in the last couple of days. I think that, like, it's the single greatest advancement in biomedicine that we're going to be able to make. And it of course is, it opens a lot of doors for us as strand because we have way more ideas than we have the resources, time and money to take forward at $50 million a try. But if you start make it more simple. And a lot of these things are common sense regulations. We're spending way too much time and way too much money doing things that I think are quite antiquated and vestigial in our regulatory process. And so if you can reduce that time and reduce the amount of money, then you can change the economics and the incentives around building new drugs and you can begin to generate more diverse data that allows you to train things like AI models on what actually makes a difference in a drug and a human. We just don't have enough data. We don't have enough diversity of data data to be able to train them nearly to the level that we want right now. And a lot of it just at the end of the day, it Comes down to like, does this do something in a human? You can do all you want in the lab, you can do all you want in mice, you can do all you want in primate studies. Whatever it is that you do, it just doesn't matter to nearly the same level until you do it with a human. And when Genentech and Genzyme were coming up in the 80s and 90s, it was a comically fraction of the cost and time that it takes to bring new medicines forward today. This isn't an impossible. We've just created a lot of weird barriers and we need to get back to a first principles way of thinking within government as well. I'm not the only person preaching that, and I'm certainly not the only one in policy that thinks about it. I'd say in America we want to be the headquarters of innovation, but a lot of other countries want to be innovative too. In Asia and in the Middle east, there are countries that are like, we can do this, we have the technology, we can make investments into the space, we can make investments into companies earlier that we think have a high leverage point in the future health. And we want to go in those directions. The United States is able to do it too. But that's it.
- [58:09]
B
If you did an 8020 analysis on the impediments and someone's like, okay, we want to streamline, but if there are 10 items on your wish list, let's pick two or three. What are those two or three?
- [58:20]
A
One I think is that we should remove the FDA from a direct permission based oversight organization on the beginning of first in human trials. So let me just explain this for like a different sort of audience right now. In order to do a clinical trial of what we call a first in human. The first time you give a drug to a human, a new drug, right? So a phase one, in order to do that in the United States right now, you need to write an ind. It's called an initial new drug application to the fda. It's very long. I think ours for our first trial was 22,000 pages long. Oh my God. It costs just to write it. You have to have professional writers, professionalized system, all sorts of very expensive things just to write it. It's millions of dollars. The studies that need to go into it are millions of dollars. The manufacturing of your drug and the associated analytics of your drug in order to be correct in the document cost millions of dollars. And this tax up and up and up and up and up. And all of a sudden this application costs you $25 million and it takes 18 months to put together. Now, in China and in Australia, two of the countries that do much faster first in human trials than the United States, they have a system where you go to something to the hospital. It's called the irb, the Investigational Review Board. In Australia, they have a lot of professional, centralized IRBs that manage multiple hospitals. And they work in like a for profit system to help companies get their procedures, like figure out whether or not they're going to be a fit for the hospital. And you still have to do that in the United States. You have to go to the, after you get the IND approved by the FDA, you then have to go to the IRBs. And so right now, since it costs so much money and takes so much time to get an IND from the fda, if you have decided to do that instead of go to Australia and go directly to the IRBs in Australia or go to China, your board wants you to essentially go to the top hospitals. Hey, if we're spending 25 million on an IND, I want you to go to MD Anderson, I want you to go to Sloan Kettering, I don't want you to go to pick a random, great, but random hospital in the Midwest. So now we have a lot of hospitals in the United States not running first in human clinical trials, which means we have a lot of Americans who exhaust their standard of care and can't get the access to drugs maybe before they are fully approved. And they're just out of options unless they want to floss to Houston or New York or Philly or something like that. And a lot of people don't if they're facing the end of life or for all sorts of reasons, people don't want to do that. And so you have Americans not having access to drugs. You have companies shoved into clinical trial sites that are already overburdened. You have IRBs at those hospitals which are difficult to deal with and also overburdened and like trying to process all the people who are trying to come through their site's doors. And, and all of this is taking place after you've spent way too much money and way too much time submitting a safety document to the FDA in order for them to approve it, when the FDA actually has a lot better things to do as well. And so all of that reeks of an inefficient system.
- [61:31]
B
So if they said, got it, problem, sounds terrible, you can author the solution. What is the alternative?
- [61:38]
A
So the alternative is to allow the hospitals and their IRBs to make that they already make the decision on whether or not to run a trial and they're assessing the safety of the data that you have on your safety as well as your efficacy and the sort of patients you want to go after. The IRB is going to assess that and make a call after you get the IND done. I think the system to transition to is what Australia calls it, is a ctn. It's a clinical trial notification system. You notify the authority, authorities, the regulators, hey, we're going to run a trial. It's not a past system. There are exceptions. Certain types of drugs still need to go through them for, like, formal approval. But for the most part, you can notify them, go to the irb. The IRB can say, yep, we think this is safe enough. And the reason that is still a very safe option, because patient safety is from a drug company perspective, from everyone's perspective, is, number one, there is nothing that will kill your company faster. There is nothing that will just make me never be able to sleep again. It would be harming patients, especially harming patients, because you are being sloppy. And the group that cares obviously cares just as much, if not more than everyone else is the hospital's review board, because the hospital does not want patients harmed or dying, God forbid, in their trials. The FDA isn't magical in their oversight of safety, but you distribute this workload across the IRBs that exist throughout the United States, and they get certified with the FDA to be able to approve this. You can centralize the IRB so that individual hospitals don't have to have their own irb. You can have all of these systems. All of a sudden you have hospitals that have the ability to attract biotechnology companies for drug trials. They're now going to invest into their infrastructure. It takes infrastructure to run clinical trials. And so the free market sort of picks up there and builds a system that I think can accelerate clinical trial management. And you free the FDA to focus on the things that matter, which is approving drugs based on efficacy and safety. That's how drugs get approved.
- [63:46]
B
So I know you got to run a bit.
- [63:48]
A
We can chat again, too. This is fun. We don't talk enough.
- [63:51]
B
Yeah, this is a juicy piece, so I want to chew on it a little bit more. Yeah, so I've funded a bunch of science in mostly New Zealand, but also in a few other countries, simply because the speed of cutting through red tape and the sheer amount of red tape is much less, but also at the same time. So that's why I would choose a New Zealand and Some of these very credible universities over doing research. No offense to Jamaica, but there's psychedelic stuff going on in Jamaica. But it's like nobody in the US gives a shit, right? They're not going to listen, it's not going to hold anyone's attention. I guess what I'm wondering is simultaneously I can look at a New Zealand and say, okay, it's mostly sheep, yeah, you have some people, but it's a lot easier to run New Zealand than it is to run the United States. So I can't just say this works in New Zealand. Copy and paste into the United States. Australia's is substantially larger. So I guess two questions. The first is 0 to 10 confidence. What is your confidence level that if policymakers got behind it that something could be done along those lines? Not necessarily even at the federal level, maybe at a state level, I'm not sure if. I mean, there's all sorts of complexity there, but what's your confidence level that something like that could be implemented in the US with this? I don't know what the timeframe would be the next five years, let's just say five to 10 years if policymakers got behind it. And then the corollary to that is, is there any competition for scientific innovation that is attractive to a company like Strand? Much like companies are moving from say California to Texas because there are certain incentives. Is there a competition for talent globally through which if the UAE wants to greenlight something incredibly quickly and fundamentally it that Strand would be interested? Or is it live or die, ride or die in the United States for any host of different reasons? I know some companies who have tried to tackle the FDA first because they're like, hey, once we have this data, we can kind of copy and paste a lot of it into the EMA in Europe, which is the sort of equivalent. I know that's a lot that I just threw out there, but what are your thoughts?
- [65:51]
A
So to answer the first question, there's a global competition for running clinical trials like this, this and actually what we are in the midst of right now is the United States massively losing to China. China has built an industrialized version of clinical trial infrastructure for first in human trials that is so efficient and massively quick that they are, they're just able to go faster and cheaper into the thing that matters most, which is first in human trials. And so the United States is actually in the process of very rapidly as a country following falling behind China. Because what started as a place for American companies to come run clinical trials to get data and then take it to the FDA and then do larger trials in the United States has now created a flywheel structure within China where now just Chinese companies run their clinical trials faster than the American companies and then bring their Chinese discovered drugs to the United States. And what happens is the capital flow, the risk capital then says, ah, these companies are more efficient. I will fund these sorts of aspects. And so there's always like state by state, we want to have biotechnology here. Every state's always tried to have it. I'd say just like AI tech, the best technologies remain in Boston and San Francisco. Just similar to tech companies might have left for Miami and Texas. But where's OpenAI? It's in San Francisco. All due respect to Austin and Miami, I love those cities. But San Francisco, it's hard to replicate those pieces. And biotechnology has largely been spread between. Boston's really dominated a lot of it for the past 30 years. Though in this new age of medicine, I'd say San Francisco is really rivaling Boston because the risk capital and the openness to radical new ideas is much higher. I think that also attracts a healthy amount of hype. No substance companies and hype, no substance founders and technologies. But I think that's a low price to pay to take some big swings at what could be transformational technologies. And I personally identify, even though I, I run a company in Boston, I love Massachusetts. I personally identify with that ethos a little bit more of like if some bullshit hype filters into this, it's worth it in order to take the correct swings at the truly big ideas. Because 1 out of 10 transformations is better than 7 out of 10 logical steps forward.
- [68:10]
B
So CTN in the US some version of that, as you described in Australia, if you were a betting man, if you were like, okay, okay, I'm going to go on polymarket and I'm going to put half my net worth on a bet. I guess I'm asking you how possible or impossible is the task of retrofitting the FDA and approval processes?
- [68:31]
A
I think again, this is not a comment on politics and this is also not a comment on a lot of different things that are happening at the FDA right now. But I will say in terms of the last 10 years of the FDA, the, the time to which they would be open to such a radical transformation. And radical in government bureaucracy's terms. Right. The thing about government bureaucracies is they very rarely cede their oversight. They will take new things to be oversight of. But like in general regulatory anything. This is the problem with nuclear energy In America for the past 30 years, like, we just tack on one more thing and one more thing and one more thing and one more thing in these cottage industries emerge to support the giant regulatory machinery. And we don't take a step back to be like, why are we doing this? At the same time, I'd say to look at the FDA right now, this is probably the most open I've seen people to the idea of, like, let's take a step back. We want the FDA to be an exceptional regulatory body. We want them to build regulatory sciences that give us ultimate confidence in, like, the drugs that we. But there are new technologies that we've been slow to implement. There have been markets that haven't been able to be fully created with technology for things like clinical trial analysis because no one was sure if the FDA would embrace them. And there are things such as, like early stage safety, which are already handled by hospitals themselves where it will take some time to make. But if I was a betting man, I'd say I give it a 50% likelihood that in the next two years we can get to this. I wouldn't be spending my time talking to policymakers about an idea. This isn't about me just trying to like, have something to complain about to like a senator. This is like a. I believe that this is possible. I believe that we can do this. I believe if we don't do it, it is actually existential. Like, we will lose like a lot of our ability to develop drugs in America over the next few years to China if we don't do it, because capital has no allegiance. I also believe that, like, there's other countries, and especially the UAE for example, are ones that are watching it carefully and going, hey, we have great technology, we have a great landing place for a lot of Western values and Western companies. We have great quality of life here. We could attract folks to come do innovative work here. And so when I hear various different leaders of countries in the Middle east talk about it, I certainly think it's possible because they are countries, at least over the last 10 years, where you've seen be able to make aggressive bets in certain directions in order to attract innovation. So if they were able to do that, then, yeah, I mean, these sorts of things could radically transform how people think about developing medicines. And at the end of the day, if we are able to develop better medicines quicker, faster, cheaper, more ambitiously, everyone wins.
- [71:23]
B
I've been so impressed with the speed at which the Department of Health in, say, Abu Dhabi or uae even more broadly speaking, but it's incredible how ambitious they are, but in addition to that, how willing they are to take big swings and accelerate things.
- [71:43]
A
That's the country we've spoken to the least in the Middle East. I will say though, I know that they have it's connections and it's spending the time trying to decide what people want to do. I'm a believer in allied countries coming together. We run our trials in the United States and Australia. I think countries have shared very similar values on the future of the world need to come together to build innovative solutions to the massive problems facing us as a human species. It's not every country though.
- [72:11]
B
No, it's not every country. Anything you want to talk about? Just before we just in the last however many minutes we have, I've actually
- [72:20]
A
taken a lot of way of responding to how you're responding to different pieces of the story.
- [72:24]
B
Right.
- [72:25]
A
I think I view it as important to sort of tell the world about this innovation and whether that means finding the large sovereign wealth of the world that are going to help us right now. We are as a company, everything is working within our technology stack. We sit here and look at these problems of like, gosh, to use a bad analogy, it feels like Sophie's Choice sometimes around like how we're going to prioritize what we're going to work on. We can't work on everything. The other overused analogy is robbing Peter to pay Paul. Right. It's like, okay, this feels like, like I wish this wasn't zero sum but I have, you know, if we look at what our technology can do today, I look across and I'm like, okay, we want to work on cancer, we want to work on autoimmune disease. But also like kidney is really interesting and oh my God, we could do so much good if we applied this in the crispr space and all of these things. And so what I've been trying to spend the last six months of my time thinking about is like what is the correct model for us to make sure we are doing our diligence of advancing medicine at the fastest rate we possibly can. There are so many different things that we could work, we strand can work on, on. We need to find various different partners sometimes that's pharma partners that are like we're interested in this disease area and it's very simple because the biotech and pharma companies work together all the time on partnerships. But I'd say what's really interesting is this opportunity, this global opportunity and this broader opportunity to say we could do all of these different diseases. We're fighting a resource constraint at all times. So how do we find other people who want to participate with us, both intellectually and with capital that can help us build various different solutions, whether that's for diabetes, whether that's for polycystic kidney disease, whether that's for all sorts of other indications throughout the world. It'll take novel models, novel scientific models, because what we are doing is scientifically novel. So we'll need different sorts of business models to think about this. But you said something earlier about my frustration with biotech's ambition sometimes, and I think it's just like, like God. The Genentech and Genzyme, people used to do insane things to try to get the Genzyme used to drive around Boston collecting placentas from the hospitals. They had a van called the Placenta Mobile. They would pick up placentas and then use them to purify a protein that they were turning into a drug for a rare disease. It was like the ultimate founder mode of, like, how do we stop this disease? And somehow we're now like, well, I don't know, what would that look like from a tpp? And if I can't think about, like, how the regular. If the FDA won't think about a proven mechanism and it's just exhausting, we gotta, like, just get our entrepreneurial pants back on and like, try to fix disease. So I've just taken the few minutes you gave me and diatribed in six different directions. But I, I, we are. There is so much cool stuff to do. There's so many, like, more interesting conversations for us to have on and off, off a recording that. Tim, I love talking to you. You're just fun, man.
- [75:22]
B
Yeah, we'll do more. We didn't even really get into the platform aspect of things. I used the SpaceX analogy of the first principles, engineering, payload, agnostic platform. We didn't even really get into the platform. Are you leaning away or leaning into the kind of programming reprogrammable language around Strand?
- [75:45]
A
I'm leaning away from the words programmable or programming within there because they get people confused about what a platform is like. In my new deck, it ends actually with this piece of what Strand is. Strand is a flywheel of various technologies, AI models, manufacturing expertise, like talent, trade secret. All of these pieces that create a flywheel of how we build platforms for areas of the body that we want to access. That's the platforms. Right? So tumor delivery is a platform. T cell delivery is a platform. We want to build more of those platforms over time. We build them as drugs, like the STX003 that's coming to the clinic this year six months ahead of schedule. That is a drug, but it is a platform for tumors. It's not a platform for everything you want to do throughout the body. And that's where people got lost. I think that's where moderna got lost. They thought that it was, you know, your tumor platform also worked for your liver, worked for the kidney. We could do everything with one platform. It's just not tr. And so what I've been trying to do is help people understand. And the SpaceX analogy kind of works well within this because SpaceX over time built different platforms for different use cases that were more and more complex and took more and more time and knowledge, and they used the learning. So Falcon 1 was able to get single satellites up that. It took them a while to figure it out, but they were able to perfect the landing and the recovery and the reusability of a rocket that wasn't all that, like, it was useful, but it wasn't super useful. Then they had Falcon Heavy. They were like, now we can take multiple things up, or we can take large payloads up, we can take astronauts up to the space station. We could do all of these things. Then they have Starship, which is. You can't start with starship. Even Elon 20 years ago, being one of the greatest fundraisers and visionaries, couldn't go, we're going to build Starship. That's our first product. You got to build the Tesla Roadster to get to the Model 3. You got to find the, like, the first minimal viable product that does matter and helps you get your feet under yourself. And that's what our first drug was. And now we're building more and more ambitious things. I don't mind talking about a platform because I can scientifically prove we have a tumor platform. I can show you the data, right? We have a T cell platform. I can show you the data of how we can swap things in for the T cell. Whatever you want to put in a T cell, we'll put into a T cell. Doesn't matter. But it's for a T cell and we want to build more platforms over time. That's where I think where we need the most help of, of like, you know, finding novel business models, partners throughout the globe who are, like, interested. I don't mind it. I don't mind it anymore because we can defend it.
- [78:17]
B
Yeah, totally. Getting satellites into orbit is different from getting to the moon, which is different from getting to Mars.
- [78:21]
A
Right? It's like, yeah. And injecting things into tumors is different than getting things to deliver to tumors autonomously through the bloodstream, which is different than getting to T cells, which is different than getting to your kidney, which is different than getting to your brain. Those are all different things. And they will be bigger and bigger opportunities for us.
- [78:36]
B
And now we get to part two. This is the second conversation with Jake. This is roughly two months later and a lot happened between the first and second recordings Jake's op ed ran. We did a ton of split testing and behind the scenes work. The conversation around clinical trials and US competitiveness reached new levels of traction, got in front of new audiences, and ultimately made its way, let's just call it metaphorically, to the Oval Office. And we will get into all of it. So this next section is a function follow up what happened after the first conversation, what Jake learned from the response, and how he's thinking about the bigger story of Strand and the future of medicine. We get into a lot of fun stuff in this section. Please enjoy. So, Jake, we first recorded brainstorming and you had a lot well formed, different approaches to messaging, and then we stopped recording. But at that point you had a pending, or hopefully pending op Ed. Could you just walk us through what transpired after that?
- [79:36]
A
We were working on the message, of course, and how to frame this so that people could digest what needs to happen and sort of both what needs to happen fundamentally, but also the urgency of it. So after that, the Washington Post actually placed it in their op ed column and it really, I think, went viral, at least through, you know, a lot of biotech and medical policy communities. I sort of saw it spread its way across as, you know, a number of people thought either I'd never heard this idea, it's a fantastic idea to start, or I'd never heard that there was this sort of pressing risk to our biomedical industrial base going overseas to China. And the US is sort of contributing to it by getting in our own way. So after that, you and I sort of spoke through, really sat down and thought about what's working with the piece. And the piece was pretty fully baked. And when you put something in the Washington Post, you don't have all the control over the full message. There are many other professional publicists and folks involved in that endeavor, which is totally fine, I'm just a lowly scientist. But at the end of the day, you and I started sitting and talking about what grabs people's attention? How do we drive people into the bulk of the message? How do we make people care so that they'll pick up the message? And that was really helpful because about a day after the op ed ran, a member of a congressional staff had reached out and said, said we're putting together a hearing on the Hill around the risk to the biomedical industrial supply chain and biomedical industry in the United States in relation to what's going overseas to China and how competition is shaping up and sort of degrading our ability to develop medicines here in the United States. And so as we sort of talked through that idea, it really helped because we saw what was working with the people piece, we saw what was confusing about the piece and we saw maybe what was maybe not bad, but what was helpful or better or caused more engagement or ABC testing. And all of a Sudden A is 90% of the click through options. And so once we sort of saw that, and I think one of the things that surprised me the most about it, maybe it shouldn't be surprising, but the opportunistic tone of like this is the problem, but we can fix it. Maybe it should be obvious, but that's the one that got us going. And so when I went down to the Hill about a week and a half after the piece ran, that's how we reframed the whole story, which is a much more productive way to get politicians to care about something. Right? If you come to them and you say everything's bad and it's burning and we're done, honestly, what is anyone going to do but reframing it and being upfront about bad things are happening, but we can fix them. It's in your power. Let's go. Was taken up very well. And so between the testimony and a number of meetings after, after that, that day around D.C. we really started to form a sort of fervor. And fast forward to about two weeks ago. The President put out his policy objectives, his legislative objectives, and in those legislative objectives, in fact, sort of the President recommends what he thinks the budget should look like and then Congress takes it up and then actually bakes it into it for policy sequencing. But in the President recommendations, there is this exact idea of removing barriers to getting early stage experimental medicines to American patients in America through FDA reform. And that's an incredibly quick turnaround for Washington D.C. which I think should inspire all of us to get more involved.
- [83:09]
B
All right, so let me add to the recap. Thank you for that. So we got on the phone. I was in Utah at the time I remember a very different background. Had our first recording, talking about the message, message spitballing stuff around. Then you published the op ed in the Washington Post. Afterwards came out and the piece, I pulled it up, very well baked, edited piece. The headline was, the US can't afford to offshore clinical trials to China. A burdensome regulatory environment is pushing clinical trials overseas. And when I saw that, I was like, okay, this may be the best of all possible options, but let's test that. And to your point point, there are a lot of stakeholders, a lot of people involved, and also people are busy. So if they've got 50 stories to put out once they've done the work on one, they don't necessarily want to go back and have to fiddle and fuss with every headline that they've put out, but internally grabbed it and had someone on my team go to a site called Pickfu. We're not going to get into the branding of PickFu, but PickFu.com, which is sort of human plus US AI helping you to split test. It could be an image. It could be the COVID of a board game in my case, or a card game. It could also be a headline. And the purpose for doing that, since people listening might think, well, if there's so many stakeholders, you know they're not going to change it. Why even bother? It's because we got five different options and you and I were texting. I was like, what do you think of these six options? And you're like, these are the two of the things that internally we'd come up with that you liked. Okay, well, let's only split test those, because otherwise, what's the point? Because the intention behind behind it is not to change the headline, but to then take messaging and emphasis that you can use in person or otherwise or on stage in terms of framing. So the fact that you had everything lined up to then have the refined story for congressional testimony and then to ultimately get to the big office, it's pretty fun. It's a really fun compression of things. Things. And I should also, I suppose, just as a recap for folks, highlight that what we ended up talking about a lot towards the end of the conversation was just not simplifying the message for people, but how do you simplify it and make it appealing for policymakers specifically? And that's how the text conversation unfolded around. And this is also for those people who are writing nonfiction books. Whenever there's a book that's like, why kids are all depressed and it's only getting worse, you're kind of like, do I really want to spend 200 pages reading about that problem? But if it's like, why kids are all depressed and it's not the only way, then you're like, oh, okay, there's actually potentially not a pot of gold at the end of the rainbow, but some type of prescription or recommendation for fixing the situation, then the response rate tends to be a lot higher. So where do things stand now? How do you feel about the messaging? And you know me, I'm like the person who likes to think of himself as smart, but nonetheless ends up asking dumb questions over and over and over again. But in terms of messaging, how happy are you with the messaging? We can obviously bat things around. And then are the policymakers still the primary target for your personal external cost? Because the regulatory hurdles and the molasses on the ground when you're trying to push things through is so slow still, compared to China or Australia.
- [86:50]
A
Let's say the idea itself from our first conversation, that was only two months ago. Not even.
- [86:57]
B
Yeah, not even.
- [86:59]
A
We sort of had this conversation. This is important. Fast forward two months. Once the President puts out legislative priorities to Congress that has the message inside of it, I'd say I'm pretty happy with that sort of timeline of movement. And I think that what we successfully did with the story was the bad part of it is like, this is happening. This is bad and driving urgency of like, this isn't A let's have 12 more hearings. This is a, we either fix this, this today, or we get comfortable with only getting all of our medicines developed in China or discovered in China, and then the United States will just pay the bill. So two months is an incredibly quick time for really any amount of legislative progress. I mean, it's still not done. It's still not baked. It still needs, you know, these things need to be codified. The FDA needs to actually adapt them. But I'd say that's a lot of positive forward progress and shaping the story around. Like, here is the solution up front, I think helped us really tie folks in. One of the things I learned in trips to D.C. over the past year is a lot of people go down and are like, complaining. People will hear you out, because that's what you do to a constituent if you're in public office. You're like, this is okay. I'm sorry that that happened. But it's really more like being a policy shoulder to cry on than getting anything done. And so going with, you know, this is a problem, problem. This is the urgency. It Needs your attention. And here is a solution or part of the solution. And moving our narrative between hacking it out with you, moving the narrative to bring the solution up front, I think helps people not tune out immediately from, like, to understand what someone's bringing you a story with. We've talked about this in larger pieces of stories, right? Which is like, how do you bring your focus and your hook up front, right? To me, it's. I like, as a scientist, I like to drill down to the whole piece and explain all the details to people and all the reasons why something is maybe fucked. And instead I think it's better to just start with like, hey, things aren't going great, but there is a solution. And then if you want now that you care a little bit and you see a light at the end of the tunnel, now we can go through the whole process. You can understand the nuance of, like, both what's happening, what we can do, and how we get to the other. The other side. It's almost like, you know, when I talk to technologists who are building other companies like mine and try to help scientists understand how to pitch even to other technical investors, the thing I always come back to is no one will learn until they care. So your first goal is to make someone care about what you're doing. Then they'll learn. Scientists are very spoiled because when you sit around with a bunch of scientists and talk science, they all come care. It's a science thing. Scientists, they're implicitly like, oh, wow, you study black holes and the gravity at the center of them. Like, that's so interesting. You don't have to motivate it. There doesn't have to be a reason. There's just the reason is, wow, like, cool. At MIT when I was there for six years, it was very spoiled environment because I'd be like, well, I'm working on, you know, the future of RNA medicine and how RNAs are programmable. And they'd go, wow, tell me more. And then you go out to an investor or, you know, have dinner with Tim Ferriss, and you got to wheel it back and be like, why does this even matter? Besides being a footnote on genetics? And I think that's always a good learning. And it's something I've gotten used to with talking about my company and talking about what we're doing. But then coming back to policy, it just helped drive it back to me that this is a fundamental truth of storytelling. Make people care about if you're trying to get something done, make someone Care, Care. Explain the problem, illustrate a solution and then help them. Then they can go a level deeper. We could talk about the specifics and the pathway there.
- [90:50]
B
Yeah, for sure. And the storytelling word is important because if you're proselytizing, if you're persuading, in almost every instance, it's going to be some form of storytelling. Right. So after the op ed came out, after you were giving your congressional testimony, et cetera, et cetera, you also sent me a few different docs. There was the investor update doc, which we may not get into great detail on, depending on how much needs to be redacted. But we can, we can always bleep it out or cut it. The second was sort of a primer on MRNA and programmable medicine, if that's fair to describe it. And one of the edit notes, which is a suggestion, I mean, I'm not right about everything, but I was like, you know what, in the second piece, there's the story of AlphaFold. And I was like, that's, that's a great place to start. Because sometimes if you begin with high concept or you begin with things that are a little abstract, it's easy for people to get lost, even if they understand it, for it to cause them to drift. And so it's like, okay, maybe start with story point, story. Or sure, you could start with a shocking stat and then lead into, here's the problem, here's the solution. There are a lot of ways to do it, but the story telling, peace. It's easy for people to forget selling, pitching board meeting, you name it. A lot of it is going to revolve around your ability to tell compelling stories. So where would you like to go next? I mean, I grabbed, of course, a whole bunch of things and before this call, sent you my kind of edit notes as images that I scanned, but also as a loom where I kind of walked through my thinking behind some of those edit notes. I wanted to actually, actually, before we move to that, make a quick note for people mentioning Pickfu. I don't have any equity in pickfu, just like saying it actually, which is like, I could make fun of the name, but it's like the fact of the matter is I just think it's hilarious to say so. The other application or value of the split testing is not just having maybe a better idea of one liners or framing that you could use in person. Because even though the headline of the op ed couldn't be changed, changed, when I then shared that article, I was able to use the Same link, sure. But I was able to use a different headline based on the split testing. And it was unambiguous. Right? It was like one or two of the headlines tested were by far and away the winners, statistically speaking. And so it's like, all right, just grab that. Because ultimately, top of the funnel, you need click through rate before people are ever going to read the piece. So let's optimize for that. But coming back to, I guess, where to go next next, you tell me, man. This is in service of whatever you think might be worthwhile to go over. So what are your thoughts when we
- [93:42]
A
move back to the longer piece that I've been just trying to organize some of my thoughts around, where I think at least a piece of the future of medicine is heading.
- [93:54]
B
The working headline is RNA Medicine and the rise of Platform Therapeutics.
- [93:59]
A
Yeah. So RNA Medicine and the Rise of Platform Therapeutics and thinking about what even introducing to the world what a platform therapy or a therapeutic platform could be, why it changes medicine, why it changes how we think about developing medicines, deploying medicines in the near term, the medium term and the long term. Right. Where are we going? What could be in the clinic next year because of this technology? What could be possible with medicine in five years? And then where are we on a 10 to 15 year time curve in terms of the what will be possible? And I've been trying to organize some thoughts around this. The way that I see the future. The policy piece of this story over the top is an important aspect of it because biotechnology and space rocket companies, I think, are actually two of the most similar industries out there. You have an incredibly long time horizon on investment, you have an incredibly high upfront investment cost and you have essentially binary outcomes, right? The the drug works or it doesn't, you get to orbit or you don't, you blow up on takeoff or you fail some early stage safety readout. Those are all very similar. What I think the rocket industry got out in front of them and Elon, as sort of the flag bearer of commercial space industry going back to the early 2000s, got out in front of this message with was how to engage policymakers to enable innovation to feedback on itself in a rapid context. And so in the 2000s, it actually was just like it is today with medicine. It was very hard to like rapidly launch rockets. It was very hard to fail or not completely succeed or just be given the privilege to take shots. Now, I want to say putting a medicine into a human is not the same as launching a rocket that is available to blow up over the Gulf of Mexico and we can salvage that. We do want to put people's lives in danger, but we do need common sense regulatory reform to enable this future of medicine. And as I sort of got to the end of that story with you and got that in front of Congress and got it into the President's legislative priorities, it turned back to this piece of where do I see medicine going? Where do I see platform therapeutics? And your feedback on what I had put together is actually helpful because one of the questions I saw in your loom was what do you mean by platform? What do you mean by infrastructure? Are these the same things? Are these different? And so maybe it's more helpful to talk about like what a platform therapeutic is to start.
- [96:25]
B
Yeah.
- [96:26]
A
So a therapeutic platform. People have been claiming medicines are platforms for 20 years in the biotech industry and they've almost always been wrong.
- [96:34]
B
It sounds good.
- [96:35]
A
The reason people like it is that theoretically, if you have a platform that is can be multiple drugs, then someone will give you a premium over the. It's like when Sweet Green went public and they were like, we're a tech company, not a salad company. We deserve a markup in our market cap. And you're like, okay, well, I mean, prove it. Maybe, I don't know. Domino's is a tech company and an infrastructure company. So it is possible.
- [96:58]
B
This is like a caffeine ketone induced like interjection. But people should go back and check out the stock charts on Domino's Pizza compared to like all the fancy tech companies and everything. It'll blow your mind, mind. So just put that aside.
- [97:13]
A
But yeah, this doesn't happen in biotechnology enough for the record. But I try to be a student of like business and innovation broadly and study like how elon has built SpaceX, how Domino's has built dominoes. That also shapes my global worldview on like, hey, biotechnology is having a rare earth metals moment, a rare earth minerals moment with China right now. That was, you know, 10, 15 years ago for the electric vehicle industry on the Domino side. Like, you look at that and you go, wow, this is an incredible infrastructure of tech. Story of pizza. That's like fine, it's fine. I'm from Illinois, near Chicago, so their pizza is like fine to me. That's the official talking point. But to like wheel it back, right? What is, what is a platform in business? But I guess what is a platform therapeutic? So in medicine going back 50 years to the beginning of biotechnology, you started with, let's design this drug and It's a molecule. It needs to be put together in a certain way. We do that in the lab, and then we take it forward, we put it in a patient, we see how it works, and we move it through clinical trials. If it's successful, then it gets approved, and then we can sell it in the marketplace, and then the company finally makes some amount of money. And the problem with that, just in terms of a, like, IRR or verticalization story, is that the company itself gets value because it learns how to do the process, but the technology doesn't build on itself. So you build one drug and you get that drug approved. The next time, you start back at square one for either a different medicine or a different type. Maybe you take some learnings that you have about that medicine, but everyone has the learnings because we do science in the open, right? Everyone sees your fda, a lot of your FDA documents, they see your medicine that you're bringing forward, they see what has. You have to publish your clinical trial results in certain forums. So you're not gaining any sort of peace by developing it, though you are as a business business. You're flexing that muscle, which is helpful, and it's helpful to have that experience as an organization, but you're not decreasing the risk of future medicines. So a platform therapeutic seeks to build a common technological infrastructure that you can build multiple different medicines off of. So an example of a platform would actually be Moderna's RNA vaccine platform platform. So people like to say this thing about the COVID vaccine, about how Moderna built a COVID vaccine in 62 days and got it into clinical trials. Sure, that's true. 62 days from the identification of the COVID antigen, the COVID sequence that they wanted to use, and then 62 days to create a vaccine for testing. But they spent 12 years before that developing this sort of technology, baseline technology, particles, RNA sequences, all these pieces to build a lot of other types of vaccines and therapeutics. And so when Covid came around, they had, you know, flu vaccine and all of these different types of other vaccines that they knew how they worked, and they were able to kind of plug and play in a Covid sequence where a flu sequence used to be, and use that in that setting. And that's very powerful in terms of speed, MRNA vaccines aside, and what everyone's piece on them is, I just think that the story of speed and the story of rollout is really important.
- [100:34]
B
Just for folks who, like me, are like, oh, God, I'm getting maybe not lost, but I'm like, Ooh, this is biotech. I don't know very much about to come back to the dominoes or let's say Uber or SpaceX, but it's like if Uber has built the infrastructure and everything necessary with Uber Eats to deliver hamburgers and things delivered through Uber Eats that aren't food. And then, and it's like, can you deliver these vaccines? It's not the best example because you're not going to be shipping these to people's homes necessarily. And they're like, sure. And then the story is in 60 days, Uber developed an entire system for delivering vaccines. It's like, well, kind of, right? But they had everything else already built that enabled them to do that. Which then for each additional quote unquote launch, not to mix the SpaceX, but they are de risking the entire endeavor and speeding it up by effectively skipping all of those steps that are already established.
- [101:36]
A
I would say biotechnology is, I think, incredibly antiquated when it comes to involvement of advanced technologies that are not biological. So when I think about what we need to realize the future of medicine, there's two different buckets. One of them are new drug technologies. So these are programmable medicines. These are different sorts of ways to think about the drug that gets injected into the person. How is that going to be more advanced, safer, more controllable, more adaptable, more personalizable? The second piece is like physical deployment infrastructure. How do we build manufacturing, small scale manufacturing and clinical supply chain chains that can deploy nationally and globally to make sure that in your neighborhood you're able to get this advanced medicine. And those are two different and important pieces to what I see the future of medicine becoming. And so on the therapeutic platform side, these are new technologies. This is what we're developing at Strand, right? We're developing various different, to use the SpaceX analogy, various different types of rockets. And so the way we're thinking about this is you have payloads, right, similar to satellites, that SpaceX is trying to get more and more fancy payloads, satellites, astronauts, eventually entire data centers or entire moon based crews into orbit in an efficient manner that's scalable for medicine. And in the same way what we're trying to solve is doing that with build the technological solutions to get these different proteins into the different areas of the body. And the reason that is such a pressing problem is that right now we have a lot of low hanging fruit, that is diseases we know how to treat, proteins that we know could do something about it, but the inability to sort of get the protein to where it needs to go. But we are accelerating our knowledge with AI, right? You have DeepMind and AlphaFold, creating the ability to design almost any protein you can imagine to do anything. You have new AI research tools that are helping us understand disease at a higher level of complexity. We're very soon going to reach a massive bottleneck of all of these different solutions that we know exist, like what to do and we can't get them where they need to go. We're going to have a backlog of satellites and no ability to get them to orbit in a scalable manner. And so it's great to have AI tools, it's great to build all this new technology. But we've now taken the bottleneck that used to be discovery and we're shifting it over into deployment and testing.
- [104:17]
B
What I'd love to just come back to in case it has changed. What are the blockers in the way of your most important responsibility as a CEO? Because it's like I want to make sure that what we're talking about is kind of in service of that.
- [104:34]
A
I think that's a fantastic question actually, because I guess what I'm saying about what medicine needs to have like a SpaceX moment, for instance, I don't think at least that it's a non obvious thing to realize. The problem is how do you actually execute it? And the reality of medicine development in the United States and how biotech companies work in the United States and the capital formation ecosystem that exists to create medicine in the United States is incredibly swung to the incentivization of making minor steps forward and of doing single things at a time. And so biotechnology actually in the US is not set up from a venture capital standpoint in a lot of ways, like technology is right in tech you have people constantly being like, I'm going to build a generational company in biotechnology, 90 plus percent of companies go, here's an idea, I'm going to take it from point A to point B, which is not point B is not commercial. Point A is this is the idea. And I think it could work. And point B is here's some evidence that it works. And at point B I'm going to sell the asset. It's very similar to how people think about like real estate development for instance. And so it's attracted almost like a private equity asset development sort of mindset.
- [105:52]
B
Sorry to interrupt, but like I try to be the muggle who's like, ooh, that's interesting. Like that's very memorable. But just like current state of biotech tech comparable to real estate development for these following reasons. But what would it look like for us to have our SpaceX moment? And why is that even relevant? That contrast is super interesting. It's the first time I've heard you say that and immediately I'm like, oh, yeah, okay, got it.
- [106:19]
A
I really think it is a capital markets problem. Let's go back to SpaceX again. Because I just love talking about SpaceX. No one would debate in 2004 maybe that if you radically decreased the cost to orbit of per kilogram, that that would not be an incredible business. That I think that that's very obvious. The question was both technologically and how could we possibly get there. Luckily we had someone who is both already extremely wealthy. He wasn't a billionaire yet at that point, I don't think.
- [106:49]
B
Which is fucking crazy to think about.
- [106:52]
A
Yeah, yeah. Elon being a lowly 130 millionaire in the 2000s and who then just put it all on black and was like, spin the wheel, Johnny, let's go. And then just shot rocket, shot rocket, shot rocket. I'm going to go bankrupt. Whatever. He's like, I'll just go back and make another zip2 and I'll do another PayPal if this doesn't work out. But by the way, I was a huge space nerd at the time and in high school following this like story and listening to like all of the establishment voices, being like, this guy is an idiot. He doesn't know what he's doing. But he had both his own capital. But the other thing about Elon that I think everyone should be able to tell at this point is he's an incredible capital formation genius. He's an incredible storyteller, which is the key, which was one of the core keys of capital formation for people listening.
- [107:41]
B
Are we talking about fundraising? Is that what that means?
- [107:43]
A
Fundraising? Yeah, it's about getting money around the idea. The ability to pull tons of dollars together around a core insane long term mission is an incredible skill set. That deep technology, which is sort of the umbrella that has space and qu computing and biotechnology like anything that is a long R and D time horizon requires. And so the capital pools, the fundraising environment that is traditional biotech really deeply struggles with the idea of long term bold idea investment. We have very few shots that are even allowed to be taken on goal. And so when I think about. Back to your original question. What is my goal as CEO who wants to not just build a better biotech widget? I don't want to build a better mousetrap to catch More mice for this one person and exit out of the company. We want to fundamentally change how we're able to build medicines. That is a long and expensive road. Even as you unlock. If we get drugs approved and we are able to get revenues by the time we're there, ideally our research engine is humming so much that even those drug revenues don't pay for all of the our. It's a constant like feed forward until you break through to the other side and all of a sudden you're staring at a trillion dollar ipo. So you have to kind of like catch that. As CEO, I think about how do we find globally the people who are aligned with that idea? And that's collaborators, it's financial support, it's people who want to think about. If you're trying to get the best irr on your dollar between here and next year, I might not be your best bet. I'm sorry, we might not be your best bet. We hope to be. We always hope to drive that original piece, but we want to be the 10, 20, 30 year massive return that people are going to see while we push medicine forward. And so those capital partners, they exist, they exist in the United States, they exist outside the United States. We want to be able to reach those folks and tell them these stories and be able to. When I think about my role as CEO as we try to actually, actually build the future and think about how do I get our story in a way that is digestible because the people who think about these things, everyone wants to cure cancer. I don't need a story behind curing cancer. I just need a story about how we're going to get there and how curing cancer is actually going to be one step on the road to solving disease writ large.
- [110:12]
B
I'm just looking through some of the summaries of the last stuff that we talked about. These are things that really, really stick out to me. And then it's like, okay, when I think of aerospace and I am not educated, I was not tracking it in the way that you were or like a Steven Jurbison, right, who's been just fascinated by this stuff since day zero. But when I think of say NASA and again, not to I don't know what I'm talking about, but I think about NASA and the government is incredibly slow moving and resistant to change because there are going to be a million different reasons. So it's like, okay, how did did not to designate Elon Musk as the paragon of all great things and archangel of capitalism, but he's done some pretty amazing stuff. Flaws and warts aside, for now he's
- [111:01]
A
the greatest currently living American industrialist. I don't know how anyone could possibly disagree with at least that piece.
- [111:07]
B
Yeah, with that piece. So with you and unlocking capital markets, capital formation to support this long term vision, there are people who have seemingly done this kind of stuff, stuff meaning patient capital, long term capital, vast quantities of money who have done this before. SpaceX I don't think would be the only example, at least in terms of training Wall street to be like, it's fine, Jeff is going to figure it out, he told us what he's going to do. Amazon is also pretty fascinating example of disciplining Wall street to be like, oh, we're the only company that analysts are going to give a pass not being profitable for 100 years. And by the way, if you break even exactly every year, that's not an accident, but pretty amazing financial planning. What do you feel like you most need to do? Is it getting on the road and delivering a concise message to sovereign wealth funds in your mind you're like, within three years, five years we outgrow the vast majority of venture capital from. And okay, maybe we step up and get some PE firms. I mean you already have some patient capital on the cap table, so what do you view as the main dominoes that you need to tip over or at least conditions you need to set so that you can execute on what you're describing?
- [112:29]
A
Let's wheel it back to one of the other great capitalists and industrialists of the 20th and 21st century, Jeff Bezos, because he actually did things very differently than how Elon approached SpaceX in terms of building a company that is incredibly complex, incredibly long term minded. But he did it in the public market and you could argue that Tesla has done that as well. And I think that there's an argument to be had there. But looking at what Amazon did, the thing I think every entrepreneur in the world should read is the correlated first public year to last year of Bezos's reign over Amazon investor letters. There's like a Google Doc link online that someone just put them all into 178 page PDF and then everyone should sit down and spend an afternoon drinking coffee and reading them, knowing what happens with Amazon. Reading 1998 through the dot com bubble burst, through the e commerce generation, through social media, through everyone coming online and you know, in our online world today and watching how Jeff puts forward his vision of the future, it both like gives you a lot of respect of course, the things he saw coming. But the thing that I respect about it as being a public company or going about building capital in that sort of a way is you need to say what you're doing in a way that makes sense for your investors. And I think for Amazon, they were incredibly undervalued until they weren't. For a very long time, Amazon was trading at like, a pretty low PD ratio. And then all of a sudden people were like, what is aws, by the way? And it was like an explosion. I mean, I think it was like
- [114:07]
B
2017 side hustle, little side hustle.
- [114:09]
A
Well, it was like, it's like 2017 or 2018. I feel like they went from like $120 a share to over 1500 dollars a share in what seemed like no amount of time. Is all of a sudden people were like, hold on, wait. Maybe owning all levels of the infrastructure and deployment ecosystem, plus the brand, plus then building your brands on top, plus also kind of owning the Internet in a way. Because what is AWS, by the way? $25 billion behemoth stuck inside this company. And they rocketed from like, I don't remember what their market cap was before that, but then, you know, to one of the largest companies in the world. And that is like everything that's great, a overnight success, 20 years in the making. But if you read the letters and you see it over time, you see them making bets, not every bet paid off, because not every bet should. But I believe it's very important. I'm saying this, Tim, because you asked, what do I think I need to do? Do I think we need to say what we're doing? And we need to say it publicly? We need to say it because it will attract partners. We need to say it because it will remind people who are on this mission with us about what we are building to. I think that obviously, if you invested in Amazon's IPO, you would have been very happy in 2014 with the performance of your investment from then to then. But then, if you invested in Amazon in 2014, you'd be very happy with the last 12 years of performance of that stock as well, because they continue, continue to make those investments. But you have to have people understanding your message and you need to say it. You say it every day like a mantra. We are changing the pace of medicine because what happens is the exit ramp comes. If you're doing things great, the exit ramp will always come. You need to ask yourself if you should get off the highway and understanding and reminding yourself about what you're building every single day day helps you understand whether or not you need to get off the highway. And I'm not saying every single person should keep their head down and try to build a generational company. When someone comes out and offers you an outsized amount of return on your dollar, like you have stakeholders, you have shareholders, you have people you have promised a piece to, and you need to be a diligent steward of their capital and be able to create value in that way. But I do think that it helps frame what is our current value value that is different than our market cap, whether we're private or public. There's a story about Amazon, I think, during the dot com boom, I think this is about Bezos where he wrote something like we are not our market cap, like across every chalkboard or whiteboard in the Amazon headquarters during the dot com bubble burst. Because obviously the tide went out on everyone who operated through the Internet because no one could discern the difference between a zero revenue, let's get the most people on our website company and at Amazon who is actually building something real. And so it's very important to understand your value in order to understand what would be an outsized near term value if an acquirer comes along, or just how we're going to build things. Because it's not about near term perception, it's about long term goal. And I like to think about this investment philosophy when I look at someone like Josh Kushner and how he's made just like this incredible, incredible run at Thrive Capital. I think when I look at some of those great investors who have made these high conviction bets, it seems like they're able to identify this moment in time for companies that is post conviction pre consensus, it is the ones who know. No, we're post conviction, we're no longer saying, can we do this? We're like, oh my God, this is going to work. But it's pre consensus because not everyone has caught on yet, or not everyone is convinced. There's a data set that insiders and technology technologists or whoever sit there and they go, oh my God, I think we're there. There's a moment, you know, if you go back and look at OpenAI or anthropic or any of these companies, there's a moment, probably in the late 2010s when OpenAI was running, where folks internally telling the story, if you listen to them, are like, oh my God, this is like accelerating. Before we got Dall e, before we got ChatGPT, before we had these tools. There was an int. Internal post conviction moment. And then of course there's the oh, wow. I think this beats the Turing Test. We're post consensus. No one is, I think, going to be able to debate that. AI is going to completely upend the way that everyone lives their life going forward. And that's the consensus moment. That's the 500 billion plus market cap moment for all of these companies. And so we need to understand where our post conviction moment is and then we need to build to bring folks around to the post consensus moment.
- [118:47]
B
One question popped into my head earlier that I wanted to ensure I didn't forget, which is. And I don't have a strong feeling one way or the other, but the moderna story is so apt in so many ways and yet there's a fly in the ointment, which is broadly speaking, but even more specifically, COVID vaccine has become so politicized that despite what any one individual might think, they may just need to fall in line with kind of party templates or whatever you might talk about, depending on who you're talking to. And I'm wondering if that has presented any problem or if it is behind closed doors and closed session. It doesn't really matter.
- [119:31]
A
Thinking about that analogy, there's probably better, and maybe not better, but like different sorts of analogies you could use there that are just less politically charged because there's no reason to wade into politically charged waters to explain these sorts of things. Another great example could just be like the original biotech story around people using technology to make insulin. We used to use pig pancreases, harvest them, grind them up, isolate the insulin, put it out. And the birth of biotechnology was around people, people taking the insulin gene, putting it into bacteria and getting the bacteria to actually make the insulin protein and then isolating the protein from there. But that actually became a platform because then what did people do? They created Herceptin and other sorts of medicines by taking other proteins and dropping
- [120:19]
B
it in growth hormone, et cetera.
- [120:21]
A
Growth hormone, exactly right. And that's like the basis of like the genesis of biotechnology. That's the Genentech story. That is, you know, also what Genzyme did. There's sort of bi coastal war between San Francisco and Boston. That's always existed in biotechnology, which I absolutely love. I think it makes things a lot more interesting and just sort of gives a good view on the cultures that set 50 years before any of us were here. But that I think is actually maybe even a more powerful story. And you know, we built those platforms and those companies built incredible value. And then we got away from it. Then we got more to like, okay, now biotechnology is a tool. Let's get back to drug development. And capital markets skated in the 90s. When pharma companies began verticalizing and consolidating, they began pulling in, you know, even the big guys themselves. You know, Bristol Myers, Squibb, bms, That's a big pharma company. Why does it have that name? Because it used to be three companies. You talk to people who worked in the 80s and the 90s, they're like, well, I used to work for Bristol, I used to work for Myers, I worked for Myers Squad Squibb. They started pulling in and then once they pulled in, they realized they were so large that they couldn't do research anymore. So they started buying small companies. And so what did our capital markets do? They started building for that acquisition. The problem that becomes on a timeline like that though, is the whole industry begins to skate where the capital at the other end of the market is pulling. And if that capital is M and A, mergers and acquisitions, buy ups from big pharma, then everyone in the innovation industry is focusing on what pharma wants
- [121:57]
B
to buy, what kind of shoes pharma wants to wear. Right?
- [122:00]
A
Yeah, yeah. What's pharma doing today? What's the M and A situation look like today? To the point where like this is an actual saying in biotechnology investing circles. It's called short the launch. It means that when a biotech company like mine has gotten a drug approved and is going to launch it themselves, actually take it commercial themselves, investors in the public market market on the whole will short that because they think a biotech company will mess it up. Because there's like, the muscle doesn't exist anymore because so few companies do it that they're like, short it. No, they're going to mess it up. They're going to miss their projection and their stock's going to dip and we're going to win. And that's just the market reacting to reality. It's not nefarious necessarily, but that sort of gives you a picture of how biotechnology has basically succumbed itself to be a little brother to the pharmaceutical industry. A pool of drugs that they can buy, which, that's wonderful. Google, buying your startup in the tech industry is a great exit for everyone involved. However, if the entire tech industry was reliant on meta, Google, Netflix, whoever buying your company, then you would see a lot weirder and less ambitious dynamics at the entrepreneurial Side, side. Because you'd just be trying to figure out what is Sundar going to do a year from now. You can't build for a select group of people's tastes. And that's the risk I think biotechnology has found itself in.
- [123:29]
B
Yeah. Are there any more recent examples? They don't have to be biotech, but outside of SpaceX, outside of Amazon. Not going as far back as Genzyme and Genentech. Although it is fun to look back at that. Particularly when you read some of these books on the birth of say Genentech and you realize it's like, yeah, this was kind of, it's top of mind, so I'll mention it. But it was kind of like Apple, right? You had this ragtag group of renegades in a garage, really flying by the seat of their pants and doing some wild shit. And as you said decades later, when everyone is contorting themselves into their probably inaccurate prediction of what the heads of Corp Dev or the CEO of big companies 1, 2 and 3 are thinking, the dynamic is just completely different. The incentives are very different, the timelines are very different. How you think about building on success to get back to the platform. It's like if every drug has to individually go from A to Z, you don't have a platform. It's like if you're kind of skipping A to M and you're starting at M. Okay, maybe you have a platform platform. I'm wondering if there are any other entrepreneurs or companies that stand out to you as having parallels to what you're trying to do.
- [124:50]
A
Before I get to that, just because you just compared Genentech and Apple. And I want to point something out too. I don't know if you know this, I don't know if anyone knows this. So Art Levinson, who was the CEO of Genentech from 1995 to 2000 and something was also on the Apple board of directors and became the chairman replacing Steve Jobs in, I don't know, 2011 or something.
- [125:16]
B
I did not know that.
- [125:18]
A
Yeah, there's a wonderful story about the read through and Art Levinston and his partnership and friendship with Steve Jobs between the two of them. They are highly, highly related companies and I think that is actually why I spend time studying, studying technology and why you see a increased interest, especially in the last five to 10 years, among traditional tech and deep tech Silicon Valley investors like Andreessen Horowitz or Playground Global, One of my investors moving into biotechnology, seeing a resurgence of this both technological and cultural outlook towards building big ideas around what we can do with technology applied to biology and human health. And that I think is really exciting. There's all sorts of examples of companies that have built things like this. I think that Tesla's a great example. Well, maybe we should move away from an Elon analogy. I don't mean to ride on Elon. I have spent a lot of time studying him. But like Apple is a great example of a company that sort of built like a core platform that solved a delivery problem. Not looking at the early Steve Jobs first tenure at the company, but when he really came back to the company, I don't remember what year that was. 98 maybe or something. He came back to the company, cut like 80% of their product offerings, refined it, created the smartphone era, upended BlackBerry in a way that was like so I mean they were hated on. But he created. That's a delivery system. That's what a smartphone is. Apple and the iPhone, the iPad, their delivery systems of all of the technology workplace that can work within them. And by creating that delivery system, your iPhone and you are going to work within our ecosystem and attacking that market by partnering with Joni I've and doing like, you know, creating a culture around it, but also creating an ease of operability created an ability for other companies to deliver their products to consumers. So many companies don't build smartphones, but they build on smartphones. That's a delivery platform that also is constantly getting better. The iPhone one, I actually just saw an iPhone one recently at a friend's house. He like still has his original iPhone One. I was like, God, your dad must have been rich.
- [127:41]
B
No copy paste.
- [127:43]
A
Yeah, no copy paste. Like this thick, man. It's this thick. It's this thick. But it's also, the screen is so. I thought it was so big, it's so small. But like each successive one increased its capabilities, increased its form factor, increased what it could do, became a better delivery system. Eventually supplanted, right. Over time you stopped using the earlier versions, but each one of course had a ton of value. And Apple delivered things to you. They sold you. They said, you know, they had the itunes store, they sold you music. They used it to deliver their own products. They were also a platform for other people to deliver their products. And that created one of the most valuable companies in the entire world. And that is you think about what creates the most value and what changes the way that we interact with the world around us. It is delivery solutions. It is being able to launch enough satellites to put Internet anywhere in the world and do that on an economical basis, it is a place where you could any sort of software and get it into the hands of almost every single person on this planet, or at least every single person in the developed world. And I think for medicine it is being able to reach any cell in the body and get the exact type of protein that we want there. And in the near term it'll be more traditional medicines. It'll be, we need to design them and then we need to create them and then we need to test them and we need to get them to patients and you need to develop for larger patient populations. But if you want to see what that sort of technology enables on a 10 to 20 year timeline, it's personalization. Because once you have a good view or a great understanding of how these delivery solutions work and you have the infrastructure, manufacturing, clinical deployment, getting to patients both across the country, across the world, then you can start to be like, well, why aren't we just building bespoke therapies right now? The economics is don't work. But the economics of Spotify didn't work in 2001. If Spotify's entire market was through your desktop computer, you could have never built Spotify. But you can when they're smartphones, you can when people always have it in their car. And so in 2011, that's a much better time for Spotify to exist as a company and really take off. Now that is, I think, where the future of medicine sort of goes towards. Right. A hyper personalization. We're starting to see people trying to, to build personalized medicine. Right now there's a story, Baby KJ that came out last year in the New York Times. Jennifer Doudna was involved a number of hospitals, they corrected a baby, but the reality of that baby's genetic problem was that the change needed to be made in the liver. And that's great for that baby. And there's other diseases that we could do that for in the liver, but we're going to run out. Kidney disease is not going to be solved in the, the liver. Neurodegeneration is not gonna be solved in the liver. And so we have to find the other solutions and then build infrastructure that creates an economically viable path forward to where bespoke medicines are possible.
- [130:46]
B
Yeah, we'll put in a link to baby KJ Sorry, I just threw in. No, it's great. Which I hadn't actually threw in a whole new idea.
- [130:52]
A
My larger piece of where I think the future of medicine is going. Yeah.
- [130:55]
B
Which I guess we're not gonna get into today. But you. You and I have texted on like, why has CRISPR not delivered on the expectations that had everybody euphoric X years in the past? But in this particular case, KJ became the first patient to receive a personalized systemic CRISPR base editing therapy, saving him from a fatal liver condition. So people can read more about that. Well, this is super fun. Nice to see you, man. Good to see you and happy to try to be helpful anytime. You know how to find me.
- [131:26]
A
It's always fun to talk to you, Tim. All right, man, take care. All right, we'll talk soon.
- [131:29]
B
Yeah, take care, buddy.
- [131:30]
A
Later, man. Bye bye.
- [131:33]
B
Hey guys, this is Tim again. Just one more thing before you take off and that is five Bullet Friday. Would you enjoy getting a short email from me every Friday that provides a little fun before the weekend? Between 1 and a half and 2 million people subscribe to my free newsletter, my super short newsletter called five Bullet Friday. Easy to sign up, easy to cancel. It is basically a half page that I send out every Friday to share the coolest things I found or discovered or have started exploring over that week. It's kind of like my diary of cool things. It often includes articles I'm reading, books I'm reading, albums, perhaps gadgets, gizmos, all sorts of tech tricks and so on that get sent to me by my friends, including a lot of podcast guests. And these strange, esoteric things end up in my field. And then I test them and then I share them with you. So if that sounds fun, again, it's very short. A little tiny bite of goodness before you head off for the weekend. Something to think about. If you'd like to try it out, just go to Tim Blog Friday, type that into your browser. Tim Blog Friday. Drop in your email and you'll get the very next one. Thanks for listening. As many of you know, for the last few years I've been sleeping on a Midnight Luxe mattress from today's sponsor, Helix Sleep. I also have one in the guest bedroom downstairs and feedback from friends has always been fantastic. It's something they comment on without any prompting from me whatsoever. I also recently had a chance to test the Helix Sunset Elite. The Sunset Elite delivers exceptional comfort while putting the right support in the right spots. It is made with five tailored foam layers including a base layer with full perimeter zoned lump bar support right where I need it, and middle layers with premium foam and micro coils that create a soft contouring feel. This spring, if you're thinking about upgrading your sleep, Helix will ship it to your door for free in the US, let you sleep on it for 120 nights and if you don't love it, their Happy with Helix guarantee makes returns completely painless. So check it out. Go to helixsleep.com Tim for 20% off sitewide that's helixsleep.com Tim for twenty percent off sitewide Longtime listeners know how important privacy is to me. In fact, my friends would call me paranoid or they used to call me paranoid and now they think I was just prescient in a sense these days you may have noticed it is a lot harder to protect privacy. Anyone can find your information with a quick search. It's shockingly easy and I've had friends and paid people to red team me to try to find my info. And what you'll notice is that shadowy data brokers quietly collect and trade your home address, phone, family members and more. It's a mess. You have to have a plan for defense and you can fight back with Incogni. That's Incogni. Incogni automatically removes your information across 420 plus data brokers with 1000 plus additional sites covered in their unlimited plan and they keep it scrubbed automatically. Deloitte has independently verified the headline numbers, in other words, 245 million plus removal requests and the company adheres to strict security standards with an A plus rating from the Better Business Bureau and with their unlimited plan. If you find your info on a site they don't monitor, say send them the link and their privacy team will handle it. Go to incogni.comtimi n C-O-G n I.comtim and use code TIM at checkout to get 60% off of an annual plan. One more time. Incog.comtim.