Reimagining Biotech with Jake Becraft of Strand Therapeutics — Tim’s Founder Kitchen

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're just able to go faster and cheaper into the thing that matters most, which is first-in-human trials. 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.'

So, Strand designs what we call next-generation genetic medicines. You have DNA inside of your cells. The DNA makes RNA copies of itself, and then that RNA makes proteins. And actually, life is all proteins, right? 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, right? 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 this 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. 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.

Another biotech CEO, Phil Strandwitz, and a... I don't know how to classify Jaime's job. He's a leading professor at the MIT...

Polymath, MIT Media Lab professor, healthcare entrepreneur, advisor to anyone who wants to know fancy things sort of guy. And then me.

Fantastic book.

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 with a patient with stage 4 melanoma. In early-stage trials, you end up with patients who have 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 the surface of their body in the skin, but they had what's called visceral metastasis, which 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 historically actually 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. What 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. You know, if it doesn't respond, you go to the next, and the doctor, the oncologist, cycles you through a number of drugs. 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, trying to help the patient stay alive. And the picture that we have, and this is in, you know, someone, if you Google our ASCO poster, which is a Clinical Oncology Conference.

ASCO. 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, you know, big results, small results. We had presented this photo there, and I had met you a little bit afterwards to show, I mean, the photo itself is quite striking, and it's in that poster.

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. Just riddled, and then no more. And one of the things as a scientist, Tim, you mentioned something earlier which was that 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 like mission to make genetic medicine work correctly for patients. One of the greatest accomplishments in that, you know, career that I've had thus far is being able to like 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 and the scale at which we're going to be able to help people. However, like that was the first time that I really felt like our science went out into the world and it took, you know, someone's grandmother and not only kept them alive, but we're a year and a half in and they still have no detectable like lesions.

There's one other bigger, you know, 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.

Yeah. So, 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 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 it 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, you know, 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, right? There's a difference between a good drug and a good product. I'd say the good drug is can someone take this and it does something like 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, right? 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 entire 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 cost, 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 because you know 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.

So 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 Squibb's 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 'self' signal that 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 success 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, you know, 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, you know, sort of 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.'

Yep. And so the issue, this is not new. This is basic science from like 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 like 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 like make this signal artificial and get 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 making 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, you know, 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 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 does 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.

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 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. I guess 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 a 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, right? 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 know, 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, you know, impact the organ functioning. 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. There wasn't one miracle patient that had that. That is a beautiful photo of that patient. 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 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 — they 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.

And 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. Right? The difference between, you know, a drug is all about does this work, and a product is about how will these patients get these drugs. 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 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 oncologists and the nurse practitioners and everyone, 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, 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'd say, in addition, the bloodstream is also a really good way to get around the body, believe it or not. Like, I mean, 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, like — it's 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, like, 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 big piece here is that, like, you know, 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 very handwavy.' Again, it's just a cheap answer, which is like 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 a simple solution. They want like, oh, it's delivery, so we'll just fix delivery. And I mean, just 30 years in, no one has a good idea about this piece. And I'd say that the thing at Strand 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. 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 [__]. It is awful. I can't believe someone funded us. I'm a huge fan of Elon Musk's, like, 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, like, thinking modality where, you know, if you take SpaceX, for example, his idea was what is the thing preventing commercial space flight? And it's dollars per kilogram, right, of launch. Like, it's just like dollars per kilogram. That's it. Like, 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, trashing rockets, these fuselages that we're just trashing 80% of it. And you go, well, like, why don't we just, like, reuse them? And people are like, well, you know, they do this, they do that. You know, they're hard to retrieve. They're in the ocean, they're floating, they can't. And he goes, he goes, 'What if they, like, land themselves?' And it's like, 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. You know, 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, right? That's, I think, a near-term piece, right? 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, 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 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 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, you know, infuse a genetic medicine that goes to the tumors, we have an instruction manual, what we call a payload, right? 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 that's coming, right? That's coming in a lot of other areas of the body. We're designing things to get into T cells so we can help, you know, temporarily influence the immune system so you could take out things like autoimmune disease and allow patients 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 we 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-principles-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 right now. We've shown this complex solution actually fixes this, like, 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, you know, 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, and those are all sorts of different sorts of folks. Those are people in policy. Those are —

I think there are people, policy leaders not just in the United States but, you know, across the globe that need to think like critically around how we are going to both handle, enable, and empower the future of medicine because things, you know, incentives, things are going to look quite differently 10 years from now than they do today in terms of the scope and the style in which we can build medicines.

Yeah. I mean, healthcare is very similar to the space industry. In 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, you know, two million people worldwide. I'm making 100,000 variants of a drug that I'm hoping to give to, you know, 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. Like 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, 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 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, right, when we started to harness the power of recombinant proteins. The Genentech book you plugged it earlier. That's phenomenal.

Genentech. Sorry. Genzyme's the Genentech of Boston. I get the two of them were like... But the Genentech book really, you know, studying the history of Genzyme. Genzyme actually had the leader Henry Termeer who was the actual quarterback I'd say of the policy innovation, you know, worked with government officials to figure out like 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 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 sort of how the state of AI is. And I read through it and I was like, you 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 like 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 an 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 vine, get cut off at their knees because just like space, space industry, it's a long time cycle to read these things out and you need capital to get there.

No, I want to hear this, Tim, by the way. It's a free communication lesson from someone much more versed in the area.

And sure, you could argue that you might have the rich people pay $10,000 out of pocket and that subsidizes it — it's sort of like Uber Black subsidizing Uber X. Like 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, right? It's probably not going to happen. And then you have people looking at like 5-MeO-DMT instead of psilocybin and stuff. And I have my own thoughts on that. But sure, it's like you look at the failure just real quick of like 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 game, 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 like 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 like an hour hypothetically, right? You can decouple the therapy. We're just looking at drug effects and lo and behold, like it's making a ton more progress, right? But the point of saying all that is that you've got the kind of SpaceX, you segue to like the holy grail and then like what if you could reprogram cells in the body, right? Like what happens? So I do love the fired-up hand-wavy delivery thing, right? Because you're like, what they've missed is — and I'm again, I'm ad-libbing here so it might be — it's like...

They're right and they're wrong. They're wrong because of reasons X, Y, and Z, right? And this is a lot of hand-wavy stuff. And like, 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, right? But then you say they are right about delivery in the sense that like if you cannot plug this into healthcare and deliver it to end patients, game over — like it doesn't matter how effective it is in an N of one or an N of five or whatever your small clinical is. And the idea — these are not necessarily in the order — but talking about like even though it's not the end goal, what if we could turn cancer into a chronic disease it can be managed, right? And it's like back in fill-in-the-blank 1980s, right? HIV was a death sentence, why? And no longer the case. Now you look at on television and it's like you see ad after ad related to some preventative but also like maintenance drugs that allow people to live with a chronic [disease]. So anyway, those are a few things that kind of hop to mind. I would be curious, I mean for policymakers, what are the things that most catch their attention whether from experience or hypothetically, right? Like what is it that actually gets their attention?

I was in DC yesterday, right? And my overarching message is sort of like there are two things we need to do better. We have 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 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, right? Because you know taking a truly innovative risk would be very difficult to underwrite for certain investors. I'd say at the other side, you know, 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, you know, 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.

Yeah. 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. I'd say policymakers tend to like that because well it comes down to like numbers and medicine is a very interesting piece in policy.

They like trying to learn about it. Like 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, right? 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 healthcare 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, you know, 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 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, you know, hospitalization, it's at least at the very least hopefully preventing you from being in the hospital. And so policymakers like those conversations.

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 op-ed that I wrote on accelerating first-in-human trials and becoming a more innovative powerhouse as a country.

I just wrote it a couple weeks ago.

And submitted it to a handful of places in the last couple of days. I think that it's the single greatest advancement in biomedicine that we're going to be able to make. And it of course 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 to 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, you know, 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 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 thing. 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, right? 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 [care] and we want to, you know, go in those directions. The United States is able to do it too but that's it, right?

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? 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, which is called an Investigational New Drug application to the FDA. It's very long. I think ours for our first trial was 22,000 pages long. 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 stacks 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 hospitals called the IRB, the Institutional Review Board. In Australia, they have a lot of professional centralized IRBs that, you know, manage multiple hospitals and they work in like a for-profit system to help companies 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. 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, you know, random — pick a random great but random hospital in the Midwest. Right? 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, you know, the access to drugs maybe before they are fully approved and they're just out of options unless they want to fly to Houston or New York or Philly or something like that. And a lot of people don't — if they're, you know, 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 sites' doors. 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.

So the alternative is to allow the hospitals and their IRBs to make the — they already make the decision on whether or not to run a trial and they're assessing the safety of, you know, 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 transition system to transition to is what Australia calls it as a CTN. It's a clinical trial notification system. You notify the regulators, hey, we're going to run a trial. It's not a pass 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 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, you know, 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. Right? 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, you know, individual hospitals don't have to have their own IRB. You can have all of these systems. And now all of a sudden, you have hospitals that have the ability to attract biotechnology companies for drug trials. Yeah. 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.

Yeah. This is a juicy piece, so I want to chew on it a little bit more.

So, to answer the first question, there's a global competition for running clinical trials like 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'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 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 state by state, we want to have biotechnology here, every state's always tried to have it. I'd say just like AI tech, like the best technologies remain in like Boston and San Francisco. Just tech companies might have left for Miami and Texas, but like where's OpenAI, right? It's in San Francisco. You know, all due respect to Austin and Miami, I love those cities. But you know, San Francisco, it's hard to replicate those pieces. And biotechnology, 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 like radical new ideas is much higher. I think that also attracts a healthy amount of like hype-no-substance companies and hype-no-substance founders and technologies. But I think that's a low price to pay to like take some big swings at like what could be transformational technologies. Even though I run a company in Boston, I love Massachusetts. I personally identify with that ethos a little bit more of like if some [__] hype filters into this, it's worth it in order to take the correct swings at the truly big ideas because one out of 10 transformations is better than seven out of 10 logical steps forward.

This is not a comment on politics and this is also not a comment on like 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 time to which they would be open to such a radical transformation — and radical in government bureaucracies 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 takes a — This is the problem with nuclear energy in America for the past 30 years. It's like we just tack on one more thing and one more thing and one more thing and one more thing and 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 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 build. 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, you know, two years we can get to this. I wouldn't be spending my time talking to policymakers about an idea to like a senator. This is like 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 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, right?

Yeah. I also believe that there's other countries and especially, you know, the UAE for example are ones that are watching it carefully and going, hey, like we have great technology, we have a great landing place for western, you know, 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 and, you know, 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.

That's the country we've spoken to the least in the Middle East I will say though I know that they have, you know, I mean it's connections and it's spending the time trying to decide like 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 that share very similar values on like the future of the world need to come together to build like innovative solutions to the massive problems facing us as like a human species. It's not every country though.

I've actually taken a lot of way of I don't know responding to how you're responding to different pieces of the story, right? I think I view it as important to sort of tell the world about this innovation and whether that means finding the large sovereign wealths of the world that are going to help us — like 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 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 6 months and 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 at Strand can work 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, you know, what's really interesting is this opportunity, you know, this global opportunity and this broader opportunity to say like 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 capital-wise, 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 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 like frustration with biotech's ambitions sometimes. And I think it's just like God, the Genentech and Genzyme people used to do insane things. 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 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 FDA won't think about a proven mechanism and it's just [__] exhausting. We got to 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 I think there are like more interesting conversations for us to have on and off recording. Tim, I love talking to you. You're just fun, man. So,

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 like what Strand is, right? Strand is a flywheel of various technologies, AI models, manufacturing expertise like talent that we have, you know, trade secret, all 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 ST00003 that's coming to the clinic this year 6 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 your tumor platform also worked for your liver, worked for the kidney. We could do everything with one platform. It's just not true. And so what I've been trying to do is help people understand it. 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. 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 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 could take large payloads up. We could take astronauts up to the space station. We could do all of these things.' Then they have Starship, right? 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 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, right? And we want to build more platforms over time. That's where I think where we need the most help 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.