Speaker 1: Pushkin. I love vaccines, I really do. Vaccines train your
Speaker 1: body to make these antibodies that protect you against deadly diseases.
Speaker 1: It's a thing you get so you don't get sick
Speaker 1: in the first place, and it's so clever and so
Speaker 1: elegant and so obviously useful. I think it is honestly
Speaker 1: fair to say that vaccines are truly one of the
Speaker 1: greatest inventions of all time, on the very short list.
Speaker 1: They've saved hundreds of millions of lives. Give me all
Speaker 1: of them, Give me all of the vaccines. But I
Speaker 1: gotta say the flu vaccine sucks. The flu vaccine sucks.
Speaker 1: It really does, And for a somewhat simple reason. The
Speaker 1: flu virus mutates so quickly that we can't come up
Speaker 1: with vaccines fast enough to keep up with it. So
Speaker 1: every year scientists develop a new vaccine, but even in
Speaker 1: the time it takes to manufacture that vaccine, the virus
Speaker 1: keeps mutating. As a result, even if you get a
Speaker 1: flu shot every year, there's still a good chance that
Speaker 1: you'll get a bad case of the flu. Last year's
Speaker 1: flu shot, for example, was only about thirty five percent effective,
Speaker 1: And so for decades now, scientists have asked a fairly
Speaker 1: obvious question, is there some way to come up with
Speaker 1: a flu vaccine that would work not just for the
Speaker 1: strain of flu that is circulating right now, but for
Speaker 1: almost all strains of flu, including strains that haven't even
Speaker 1: evolved yet. I'm Jacob Goldstein and this is What's Your Problem,
Speaker 1: the show where I talk to people who are trying
Speaker 1: to make technological progress. My guest today is Jacob Glanville.
Speaker 1: He's a bioengineer and an immunologist, and he's the founder
Speaker 1: and CEO of Centivax, a company that's trying to make
Speaker 1: a universal flu vaccine, a flu vaccine that will consistently
Speaker 1: and reliably prevent people from getting the flu.
Speaker 2: You imagine talking to a generation that didn't have flu anymore.
Speaker 3: They would think we were nuts.
Speaker 2: They were just like, oh, yeah, every year we have
Speaker 2: a circulating pandemic and then six months later there's another one,
Speaker 2: and yeah, you know, fifty thousand people die.
Speaker 3: But what do you do? And like, that's nuts, But
Speaker 3: we take it for granted.
Speaker 1: The vaccine that Jacob's company, Centivax, is developing for flu,
Speaker 1: is likely to go into human trials next year. The
Speaker 1: company is also in earlier stages of developing universal vaccines
Speaker 1: for HIV and COVID, among other diseases, and wildcard. They
Speaker 1: have also worked on creating a broadly effective anti venom
Speaker 1: for snake bites. We talk about snake bites later in
Speaker 1: the conversation. To start, Jacob told me about the moment
Speaker 1: he first got the ia for a universal vaccine. It
Speaker 1: was around twenty twelve. He was working for the drug
Speaker 1: company Feizer, and he wasn't working on vaccines, but he
Speaker 1: was doing something related. His job was to identify antibodies
Speaker 1: that could be used to treat disease, and at this
Speaker 1: particular moment, he was studying antibodies that would bind to
Speaker 1: a particular protein called PCSK nine.
Speaker 2: And so I was riding back on my motorcycle one
Speaker 2: evening and I was reflecting on this problem where there
Speaker 2: was this target called PCSK nine. It kind of looks
Speaker 2: like Mickey mouse's head, and they really wanted antibodies against
Speaker 2: kind of where the neck is that if you get
Speaker 2: an anybody there.
Speaker 3: Then that can affect cholesterol and lower cholesterol.
Speaker 2: The problem is that they're getting anybodies against the ears,
Speaker 2: and they weren't getting anybodies.
Speaker 3: Against the neck.
Speaker 2: And so I was trying to figure out, is there
Speaker 2: an engineering way to sort of focus the immune system
Speaker 2: at arbitrary sites that would save me a bunch of time.
Speaker 2: And I started imagining, what if I were to take
Speaker 2: that target not just from humans, but from like a
Speaker 2: donkey and an alligator and a chicken, and like just
Speaker 2: take a swath of different versions of that. They were
Speaker 2: different just about everywhere up in the ears, but they
Speaker 2: were the same down where the neck was.
Speaker 1: Huh.
Speaker 3: And then if I.
Speaker 2: Mixed those together and diluted each one so there wasn't
Speaker 2: enough of any one of the species of PCSK nine,
Speaker 2: then maybe only the neck would be the thing which
Speaker 2: was shared across all of them, and the entire immune
Speaker 2: system would focus on uh huh.
Speaker 1: So like in total, the sort of sum total of
Speaker 1: the mix, it would be like a lot of neck.
Speaker 1: The neck is conserved. The neck is what is the same,
Speaker 1: and there's only enough of that to induce the antibody response.
Speaker 1: So that then if you whatever inject that into an
Speaker 1: animal or a person, what the person's immune system is
Speaker 1: going to see is a lot of neck.
Speaker 2: Yeah, And so they finally focus on the neck instead
Speaker 2: of getting distracted by the ears. That was the principle,
Speaker 2: And so I got home, and then at a certain
Speaker 2: point I realized I was being an idiot and what
Speaker 2: this was was not a way to save a few
Speaker 2: months on an Anybody discovery campaign, that this was a
Speaker 2: potential window opening to the to the.
Speaker 3: Holy grail of vaccine science.
Speaker 2: The holy grail is that all of the major viruses
Speaker 2: that we're confronted with flu, influenza, HIV, ebola, these viruses
Speaker 2: mutate and change, but they always have some little spot
Speaker 2: that they cannot mutate. And those spots are always super important.
Speaker 2: That's why they can't mutate it because if you mutate it,
Speaker 2: the virus.
Speaker 3: Is no longer infectious.
Speaker 2: Yeah, And normally they get away with it by having
Speaker 2: distracting areas and most of the surface that can mutate.
Speaker 2: And that's why we have to update our flu shots
Speaker 2: every year.
Speaker 1: Distracting meaning distracting to our immune systems, like our more
Speaker 1: immune systems. Ooh, I like the ears. I like that
Speaker 1: shiny part on top, and that's exactly Yeah.
Speaker 2: Basically, the conserved Achilles heel is a small site and
Speaker 2: most of the surface can vary, and it can't it
Speaker 2: gets away with not changing the critical site by varying
Speaker 2: lots of stuff around it and taking advantage of the
Speaker 2: fact that the immune system doesn't know the difference, and
Speaker 2: so to the ability to focus the immune system against
Speaker 2: a conserve site would be the basis of a universal vaccine,
Speaker 2: because instead of targeting one strain of flu or one
Speaker 2: strain of coronavirus or one strain of HIV, you could
Speaker 2: target the shared sites that the virus is never allowed
Speaker 2: to mutate. And if you do that, then you're suddenly
Speaker 2: hitting the entire class of influenza viruses, including future ones
Speaker 2: that haven't evolved yet.
Speaker 3: Right.
Speaker 1: I mean that part of the idea is the part
Speaker 1: everybody knew already, right, Like that is the relatively obvious idea.
Speaker 1: It's like, don't go for the part that changes, go
Speaker 1: for the part that's the same. Right. The hard thing
Speaker 1: is how do you do that? So had when you
Speaker 1: described the idea of like, oh, just take a bunch
Speaker 1: of different ones, dilute them, mix them together. Nobody had
Speaker 1: thought of that before.
Speaker 2: Yeah, so surprisingly not to your point, people since the
Speaker 2: nineties were aware of these conserve sites, and so they
Speaker 2: knew where the sites were.
Speaker 3: We had crystal structures it was just, how the hell
Speaker 3: do you get the immune system focus on those sites?
Speaker 3: Was the problem. Yeah, and people have tried a couple
Speaker 3: different things.
Speaker 2: They tried chopping out parts of the protein, but then
Speaker 2: the site you're interested in falls apart. It's like trying
Speaker 2: to grab a snowflake. It'll melt in your hands. They
Speaker 2: tried a couple other techniques that didn't work out.
Speaker 1: So okay, so you have this new idea for how
Speaker 1: to make a universal vaccine that nobody's tried before, which
Speaker 1: to use flu for an example, would mean you take
Speaker 1: a bunch of different strains of flu, and in particular
Speaker 1: the sort of spike protein of the flu that your
Speaker 1: immune system sees. Then you dilute them and mix them
Speaker 1: all together in a single vaccine. So what the patient's
Speaker 1: immune system winds up seeing the most of is the
Speaker 1: part that's the same in all those different strains, the
Speaker 1: part that doesn't change. And then ideally the patient will
Speaker 1: develop antibodies to that part, the part that doesn't change,
Speaker 1: and therefore the patient will be immune to like almost
Speaker 1: any strain of flu.
Speaker 3: Yeah, and you recognize it might not work right.
Speaker 2: You always are like, look, this is a pipe drain,
Speaker 2: but like I could not go to sleep because I
Speaker 2: was like, if this works, this is such a stunning
Speaker 2: breakthrough that it's like it's hard to sleep when you're
Speaker 2: thinking about that.
Speaker 3: It sort of becomes all consuming.
Speaker 1: So you get this idea, and you're working for Pfeiser,
Speaker 1: a company that makes vaccines. By the way, what do
Speaker 1: you do?
Speaker 3: Yeah?
Speaker 2: So again, I was not doing anything involving their vaccine group.
Speaker 1: I was doing for intellectual property reason.
Speaker 3: Ye. Yes, I was not working on vaccines at Pfizer.
Speaker 3: I resigned. So I did two things.
Speaker 2: I started my first company, Distributed Bio, and I also
Speaker 2: applied for the PhD program in immunology at Stanford.
Speaker 1: And you do this because of your idea?
Speaker 3: Yeah?
Speaker 2: Yeah, Because basically I applied to the PhD program because
Speaker 2: I was like, if I'm wrong, I need to stop
Speaker 2: thinking about this. I need to surround myself with brilliant
Speaker 2: immunologists who can kick holes in this, and I need
Speaker 2: to be able to make sure I'm not being myopic.
Speaker 3: And then if I'm right, I need the world to
Speaker 3: hear me.
Speaker 2: And so I need to be a card carrying PhD
Speaker 2: immunologists from Stanford so that people go, Okay, this guy
Speaker 2: is into some Yahoo and then for the company side,
Speaker 2: I just saw this opportunity to be able to go
Speaker 2: test it because I originally I did go out and
Speaker 2: I try to talk to some vcs in twenty twelve,
Speaker 2: and I think there, you know, predictably, their answer is like,
Speaker 2: what the hell is this?
Speaker 3: And who the hell are you?
Speaker 1: And you were a bachelor's degree, right, we'd worked at
Speaker 1: Miser for a couple of years, like a million other people,
Speaker 1: so not you.
Speaker 3: Know, you can't blame him. I was like, I guess
Speaker 3: I'm nobody right now. Let me go fix that.
Speaker 2: Yeah, And so I decided that I was going to
Speaker 2: go found a company because there was some work I
Speaker 2: was doing at Pfeiser that i'd public created some publications
Speaker 2: on using the deep genomic sequencers to look at the
Speaker 2: immune system and then building better anybody libraries with what
Speaker 2: we learned about that, and I realized there was a
Speaker 2: business that could be built on that. And my intention
Speaker 2: was to build that business and use it to subsidize
Speaker 2: some of the early proof deep risking experiments.
Speaker 3: On this universal vaccine concept. And so that's what I did.
Speaker 2: So I just did both for five years and didn't
Speaker 2: sleep that much until the PhD. Graduated from that, and
Speaker 2: then later I sold the first company distributed by it.
Speaker 1: So the company you start you're selling your clients are
Speaker 1: drug companies essentially, right, But you're doing that that's sort
Speaker 1: of your side hustle. That's sort of funding your vaccine dream. Right.
Speaker 1: And while you're doing that, you start doing this research
Speaker 1: on your vaccine in pigs in Guatemala, right, tell me
Speaker 1: about that.
Speaker 2: The background is I grew up in Guatemala. My parents
Speaker 2: are Americans, but they met in Guatemala in the seventies
Speaker 2: and they built this hotel and restaurant with my grandmother.
Speaker 1: Hippie dream.
Speaker 3: Yeah, the hippie dream, that's exactly what it is.
Speaker 2: There's small hippie enclaves down there, and then there's most
Speaker 2: of the village is the wheel may In and then
Speaker 2: there's Katchi Kels and some other Mayan communities, and it's
Speaker 2: very beautiful lake. So it makes sense that the hippies
Speaker 2: would go there.
Speaker 3: The Civil War largely.
Speaker 2: Drove them away, but my family, when I was a
Speaker 2: little boy, they went down there to try to fix
Speaker 2: up and sell the property. And then one thing led
Speaker 2: to another and we ended up becoming innkeepers.
Speaker 3: And so I grew up in the village.
Speaker 2: I think it probably had an effect on my interest
Speaker 2: in immunology in the first place. And I had this
Speaker 2: connection to Guatemala, and I ended up maintaining a connection
Speaker 2: to USAK, which is the University of San Carlos, the
Speaker 2: National University. And so fast forward in my career too,
Speaker 2: when I was thinking about universal vaccines, like one of
Speaker 2: my I say, one of my deep impressions left from
Speaker 2: some work adviser was this. I was very impressed with
Speaker 2: a group that was doing animal health work because I
Speaker 2: felt like, instead of using mice, they would often ask
Speaker 2: what's the most relevant and similar animal model to humans
Speaker 2: for this indication? Mouse is not a person like no
Speaker 2: animal as a person, but you can find something that's
Speaker 2: a closer fit and waste less time on failed translation.
Speaker 2: And so I liked I had this technology. I was
Speaker 2: trying to figure out where to apply it. I actually
Speaker 2: called one of the guys and I was like, what's
Speaker 2: the venor market that has a rapidly mutating pathogen that's
Speaker 2: also found in humans?
Speaker 3: And he said, it's definitely flu in pigs.
Speaker 2: They get the flu in fact they transmitted to humans,
Speaker 2: and so pigs are definitely not as convenient as mice,
Speaker 2: but I felt that the data would be much more
Speaker 2: meaningful because they actually get the flu.
Speaker 1: Yeah.
Speaker 2: So I ended up doing it back in Guatemala with
Speaker 2: Airwin Calagua, my collaborator at the University of San Carlos,
Speaker 2: and some property that my father had. So I ended
Speaker 2: up making some calls. I found out we could get
Speaker 2: the pigs. There was a vet who was involved in
Speaker 2: the H one in one two thousand and nine pandemic
Speaker 2: shift monitoring.
Speaker 1: You're doing it in Guatemala because it's cheaper. Basically you're offshoring.
Speaker 2: You're yeah, it's way cheaper, radically cheaper and faster. I
Speaker 2: think if the cycle time is astonishingly slow to do
Speaker 2: animal studies and ask for grants like you're lucky to
Speaker 2: get a study done like once every two and a
Speaker 2: half years according to the US model, Whereas in Guatemala
Speaker 2: the costs were radically cheaper. I could build a facility
Speaker 2: to spec and I was, you know, I'm an engineer,
Speaker 2: so I need to be able to do cycle yeah. Yeah,
Speaker 2: and so this enabled me. I think we ran five studies.
Speaker 3: There over a couple of year period.
Speaker 2: We're able to go pretty quickly go in and do
Speaker 2: rapidly de risk this universal vaccine technology in a way
Speaker 2: that was economically feasible given the growing profits but still
Speaker 2: finite profits that I had from the Anybody discovery and
Speaker 2: software side of the business.
Speaker 1: So when you're doing those pig studies, I mean just
Speaker 1: to return to your initial idea of using essentially different
Speaker 1: different strains. Let's say you got to figure out what's
Speaker 1: the right concentration, because if you do too little, it's
Speaker 1: you don't get any meaningful immune response, and if you
Speaker 1: do too much, then you're getting immune response to the
Speaker 1: parts that are not conserved, to the parts that you
Speaker 1: don't want immune response to exactly.
Speaker 2: I was just just proving the concept right because I
Speaker 2: think there's definitely people who are like, this isn't going
Speaker 2: to work.
Speaker 3: There's no way.
Speaker 2: And look, if I'm wrong, then if it doesn't matter
Speaker 2: if I put fifteen things in, if each one's below
Speaker 2: the dose and they're not interacting like I was hypothesizing,
Speaker 2: then you should see no immune response.
Speaker 3: Right, So I could have just been wrong. That's the
Speaker 3: other thing I was testing, does the principle hold? And
Speaker 3: the answer was definitively yes.
Speaker 1: So okay, So you have this idea that it works
Speaker 1: somewhere around here, you sell I don't know which one
Speaker 1: is the side hustle and which one is the main hustle.
Speaker 1: I guess vaccinating pigs in Guatemala sounds like a side hustle,
Speaker 1: even though it's the thing you really care about. Right,
Speaker 1: you sell distributed bio and you've spin out sent to
Speaker 1: vax the vaccine company, right, and then what then where
Speaker 1: are you?
Speaker 3: Yeah? So it was a good time.
Speaker 2: So we got the Gates Foundation awarded us this in
Speaker 2: the Pandemic Threatgrand Challenge award to test the vaccine no
Speaker 2: longer in Guatemala, but up in American facilities that had
Speaker 2: biosafety containment, so that we could challenge the animals who've
Speaker 2: been vaccinated with these strains that had evolved after the mixture.
Speaker 2: So we deliberately pretended it was two thousand and seven
Speaker 2: and only included strains up to two thousand and seven.
Speaker 2: Then we challenged the animals with the two thousand and
Speaker 2: nine pandemic shift virus, a twenty twelve a twenty seventeen virus.
Speaker 1: That's a big question, right, It's like testing something that's
Speaker 1: out of the model, right, Like it's saying, Okay, we
Speaker 1: give somebody this vaccine and then there's a new kind
Speaker 1: of flu. Does it work? Yeah? Yeah, And it.
Speaker 3: Felt that that was essential.
Speaker 2: By the way, those same pigs we pulled their serum
Speaker 2: out of the freezer over the last couple of months
Speaker 2: and they neutralized the H five and one that's currently
Speaker 2: outbreaking in cows and chickens and some people.
Speaker 1: Huh the bird flu.
Speaker 3: The great super broad immune response.
Speaker 2: So the timing was good. CR wanted to buy. I
Speaker 2: was happy to do it, and my condition was I'm like, look,
Speaker 2: I want to take this universal vaccine technology with me
Speaker 2: to a new company, and they agreed to that. That
Speaker 2: was December thirty first, twenty twenty is when when the
Speaker 2: sale completed, and so basically January first.
Speaker 1: That is a remarkable time to go all in on
Speaker 1: a universal vaccine. December thirty first, twenty twenty.
Speaker 2: We transitioned over January first, twenty twenty one. I'm now
Speaker 2: the CEO and founder of Cinevacs, and I started calling
Speaker 2: an army of geniuses of the best people that I've
Speaker 2: worked with to gather together, and I was like, look,
Speaker 2: this is going to be the big one.
Speaker 1: Where like a like a heist movie, like, oh it's eleven.
Speaker 3: Yeah, it was like the best people of my entire
Speaker 3: career I worked with.
Speaker 2: You don't need a lot, you just need every person
Speaker 2: to be exceptional, and like, if we do our jobs right,
Speaker 2: we touched the long arch of history.
Speaker 1: Yeah, so what have you figured out? Like, what have
Speaker 1: been the key things you've figured out? Since then?
Speaker 2: We identified a couple extra people we brought in, including
Speaker 2: Jerry's Sadoff. He's this guy who has more vaccines approved
Speaker 2: than anyone alive. So things like guarda cel MMRV that
Speaker 2: all children take. You have the coronavirus vaccine from J
Speaker 2: and J the one shot, and you know, I think
Speaker 2: fourteen vaccines have been approved under his watch. It wasn't
Speaker 2: just that he had done a huge amount of like
Speaker 2: the modern vaccines that define the modern health era. It's
Speaker 2: that his hit rate was unusually high, Like it wasn't
Speaker 2: like he worked on one hundred get to those fourteen
Speaker 2: he had, Like his ratio of success.
Speaker 3: Was unusually high.
Speaker 2: And that told me I wanted to work with them,
Speaker 2: And so I called them up and went out to
Speaker 2: have dinner with them, and I was like, Jerry, you
Speaker 2: told me this universal vaccine technology is the only thing
Speaker 2: you thought was worth a damn like, come join me
Speaker 2: and like, let's kick a hole in the universe. And
Speaker 2: so he came. And the reason I'm telling you this
Speaker 2: is that he didn't just come in with phenomenal clinical plans,
Speaker 2: which he did. He also came in with some strategies
Speaker 2: where he's like, one of the things I've noticed for
Speaker 2: both the coronavirus vaccines and the RSV vaccines was that
Speaker 2: the folks who added in little mutations to keep those
Speaker 2: spikes stable, those vaccines were successful, and the folks who
Speaker 2: didn't add in good stabilizing mutations their vaccines were unsuccessful.
Speaker 1: Huh.
Speaker 2: And he said, I think that that's just a critical thing.
Speaker 2: You want to trap these spikes in their stable forms
Speaker 2: so the immune system can target what the spike looks
Speaker 2: like before it a tax a cellar before it falls
Speaker 2: apart to confuse the immune staff.
Speaker 1: So, just to be clear, like the spike proteins, it's
Speaker 1: the hema glutenants that are in nature on the outside
Speaker 1: of the of the of the flu virus. They have
Speaker 1: a three dimensional shape, right, Yeah, they can change three
Speaker 1: dimensional shape, and that actually turns out to be important
Speaker 1: for sort of simple mechanical like a key fitting into
Speaker 1: a lock. Reason right, and it's and they don't if
Speaker 1: you rip them off the virus as you are when
Speaker 1: you're presenting them in this vaccine necessarily stay in the
Speaker 1: shape you want them to stay in. That's a o.
Speaker 2: They're kind of like a little three prong grappling hook
Speaker 2: and they change shape in order to like hook into
Speaker 2: the cell membrane and then tear it open. And they're
Speaker 2: designed kind of like with hinges because they need to
Speaker 2: be able to be mobile and make changes. And so
Speaker 2: this protein is not inherently stable, but what you want
Speaker 2: is you want the thing very stable because you want
Speaker 2: the immune system to train on defeating the trimer when
Speaker 2: it's in it's sort of cocked and loaded, but prior
Speaker 2: to shoot position. And we've seen with RSV and coronavirus
Speaker 2: that that was absolutely essential for the successful vaccines.
Speaker 3: And so anyway, Jerry came in was like, we should
Speaker 3: do this with flu.
Speaker 2: I had a bunch of experience stabilizing proteins from work
Speaker 2: we did stabilizing antibodies Advisor and then also at my company,
Speaker 2: a distributed bio and so we ran a quick campaign
Speaker 2: and we identified these great stabilizing mutations and they had
Speaker 2: like a pretty stunning effect on the quality of the
Speaker 2: immune response.
Speaker 1: So you're doing this basically atomic level engineering of the proteins, right,
Speaker 1: yeah's the thing. Go on? What else?
Speaker 3: And then the other thing.
Speaker 2: The major thing we've done is we started the manufacturing,
Speaker 2: we advanced the program not just for flu, but we're
Speaker 2: also we have data validating the universal coronavirus vaccine, We're
Speaker 2: testing on HIV, we're testing on a malaria and a
Speaker 2: number of other pathogens right now to.
Speaker 3: Be able to create a portfolio. So those have been
Speaker 3: some of the major activities in the last couple of years.
Speaker 1: When are you doing human clinical trials?
Speaker 2: Yeah, so we've got about nine months left of manufacturing
Speaker 2: or eight months of manufacturing, and then you spend a
Speaker 2: month getting permission from the FDA to start your study
Speaker 2: and then we'd start human trials.
Speaker 1: So okay, so next year you're starting human trials. Next year.
Speaker 1: So when you think about the future, the future of
Speaker 1: the company, of your work, like, what are you worried about?
Speaker 2: So I worry about less and less things, and then
Speaker 2: the things I worry about evolve. So in terms of
Speaker 2: is it going to be safe. I worry about that
Speaker 2: extremely little. We have been vaccinated with influenza HA protein
Speaker 2: since the nineteen forties. It's actually the best validated, diverse
Speaker 2: class of versions of HA compared to any other vaccine
Speaker 2: that's been tested.
Speaker 3: And it's that's all. The history of safety has been
Speaker 3: extremely good. We're using the.
Speaker 2: Advisor Biointech mRNA chemistry, so you can get a non
Speaker 2: exclusive license to it.
Speaker 1: That's the same one they used for the COVID vaccine.
Speaker 2: Yeah, it's been in billions of people, so we know
Speaker 2: what the safety profile is. So safety I'm not concerned
Speaker 2: about in terms of efficacy, like how well it works.
Speaker 2: I basically don't believe in any one animal's immune system
Speaker 2: because you could always overfit the immune system, could overfit
Speaker 2: in a certain bizarre and unpredictable way. And so we've
Speaker 2: tested this in pigs, but also ferrets, also rats, also mice,
Speaker 2: also cows, and also human immune organoids, which is organ
Speaker 2: donors offer their lymph nodes. They're smashed up and you
Speaker 2: basically create a bunch of little mini lymph nodes from
Speaker 2: a donor and you can vaccinate them under different conditions
Speaker 2: to see how someone with a lifetime of immune memory,
Speaker 2: including deflu and vaccines, would respond to our vaccine or
Speaker 2: a control vaccine. And when we did that as well
Speaker 2: as all the other animals, we consistently saw this universality effect.
Speaker 2: And so going into the human trials, I think we're
Speaker 2: pretty bullish that the effect is going to be dramatically
Speaker 2: better than the current vaccine. So I think we're going
Speaker 2: in assuming that the human trials probably will perform well.
Speaker 3: But I honestly I won't sleep well at night until
Speaker 3: I get that data and I'm like, Okay, yeah, we're
Speaker 3: on solid footing.
Speaker 2: We've done everything I can to de risk it with
Speaker 2: these other organisms and even human immune organoids, and now
Speaker 2: it's time to run it in humans.
Speaker 3: Fundraising is always a headache where we've got.
Speaker 2: Now at least multiple groups gathering around with sheet options
Speaker 2: and we're looking at them. But it's it's been, just
Speaker 2: to put it lightly, a difficult period for biotech fundraising,
Speaker 2: and we've managed to survive where a number of other
Speaker 2: companies have not. But you know, I've probably gained some
Speaker 2: gray hair and probably you know, took away some of
Speaker 2: my health span as a consequence of surviving this period.
Speaker 1: I mean does that last thing mean you're afraid of
Speaker 1: running out of money? That's what I mean.
Speaker 3: Every company worries about that. That's the nature of adventure.
Speaker 2: We've managed to pull it together and we just got
Speaker 2: this grant which covers us. But the fear is that
Speaker 2: we're stuck, that we need to go continue raising money
Speaker 2: so that we can go pay for the rest of
Speaker 2: manufacturing and pay for clinical and and armed for the
Speaker 2: next parts. And to be blunt, this has been an
Speaker 2: absolutely terrible period in biotech. So we got seventy five
Speaker 2: percent off on all of our equipment for my entire
Speaker 2: laboratory because we got it from auctions. A lot of
Speaker 2: this stuff was in like new stuff in boxes where
Speaker 2: a company just ran out of money and they're stuck.
Speaker 3: And you know, I've benefited from it.
Speaker 2: I've benefited from being able to hire remarkable people that
Speaker 2: otherwise we're struck to find an opportunity because of it's
Speaker 2: we've basically lived in this like a little bit of
Speaker 2: a biotech hangover after I think there was too much
Speaker 2: investment and sometimes in some pretty goofy stuff during the
Speaker 2: pandemic for biotech, and I think we're in this like
Speaker 2: a little bit of a headache, a little bit of
Speaker 2: a macro economic global uncertainty area, and those things are
Speaker 2: both slammed up against biotech in an unproductive way.
Speaker 1: Yeah, it's okay. What's the happy version of the story.
Speaker 2: The happy version is that our vaccine works the same
Speaker 2: as it has in all those animals and organoids that
Speaker 2: we've seen. We bring it forward universal vaccine just becomes
Speaker 2: the vaccine because that's suddenly a vaccine that you take
Speaker 2: and you don't get sick. The first thing it does
Speaker 2: is it creates a massive improvement in global health. And
Speaker 2: then the major impact of you know, flu kills people, right, It.
Speaker 3: Gets a lot of people sick. People lose a lot.
Speaker 2: Of time from school, pregnant women in their second trimester
Speaker 2: to get flu, or seven times more likely to have
Speaker 2: a child with schizophrenia and they're adult.
Speaker 3: Like. There's a bunch of like squali and consequences.
Speaker 2: But the biggest effect is that when this gets out there,
Speaker 2: the pandemic era is over.
Speaker 1: And when you say pandemic you mean flu pandemic.
Speaker 3: Yeah, the flue pandemics are over, which is our most
Speaker 3: common source of pandemics. We had five in the last
Speaker 3: hundred years. We had two or three per century before then,
Speaker 3: so they got faster. We have a lot more people.
Speaker 2: We have these pig megafarms, like we need to fix this.
Speaker 2: And with this vaccine, you no longer have a pandemic
Speaker 2: era because you have a decent proportion of the population
Speaker 2: that's already immune to the new virus strains before they hit.
Speaker 2: And that's what the new world looks like. And so
Speaker 2: that's the happy version for flu. But our intention is
Speaker 2: to do that for every pandemic pathogen, to just one
Speaker 2: by one go and in the pandemic era, to come
Speaker 2: up with countermeasures that first protect the world from pandemics
Speaker 2: the medical, personal, and economic costs. Second protect the world
Speaker 2: from just major outbreaks. And then ultimately I want to
Speaker 2: have these same tools can arm future decade to attempt
Speaker 2: eradication campaigns that previously.
Speaker 3: Were not possible. And that's the future we want to build.
Speaker 1: We'll be back in just a minute. Let's talk about
Speaker 1: snake bites.
Speaker 3: All right, let's do it.
Speaker 1: How'd you get into the snake bite business?
Speaker 2: Yeah, so it was twenty seventeen, and I think it
Speaker 2: was because the World Health Organization was announcing, you know,
Speaker 2: the neglected tropical disease nature of snake bite, kind of
Speaker 2: declaring it a neglected tropical.
Speaker 1: Disease, basically saying, hundreds of thousands of people are killed
Speaker 1: or very badly wounded every year by snake bites. It's
Speaker 1: not just some weird thing, and not enough.
Speaker 2: People are trying to develop countermeasures.
Speaker 1: And I think what had happened because most of the
Speaker 1: people who are who die or are severely injured are
Speaker 1: super poor.
Speaker 3: Yeah, yeah, that's.
Speaker 2: It reminds me of a Mandy python where they have
Speaker 2: the Roman Senate and someone goes.
Speaker 1: What do we do about the poor?
Speaker 3: And then all in unison they put up their hands.
Speaker 3: They're like, fuck the poor, all right, next.
Speaker 1: That's a neglected tropical disease story.
Speaker 3: And the fundamental problem. Yeah.
Speaker 2: I think also that I'm to be fair, I don't
Speaker 2: know to be fair, but like the companies that make
Speaker 2: anti venom, most of them are kind of doing it
Speaker 2: as a public service, as a loss, because most of
Speaker 2: the people who need anti venom, of the millions of
Speaker 2: bytes per year, they're poor. They're subsistence agriculturists and their
Speaker 2: children and people who live in rural environments. And if
Speaker 2: you take that market, which is probably like five to
Speaker 2: six hundred million total per year, but it's fractured across
Speaker 2: thirty to forty products. Each of those things is pretty unattractive.
Speaker 1: Just to be clear, because you need different anti venom
Speaker 1: for different snakes different Yeah, there currently is.
Speaker 3: No universal anti venom on the market.
Speaker 2: So people had started ending programs to make certain types
Speaker 2: of anti venoms, and I think that was happening in
Speaker 2: twenty sixteen. So then in twenty seventeen the World Health
Speaker 2: Organization brings some attention to this, and then I started.
Speaker 3: Thinking about it.
Speaker 2: I you know, in my village we had snake bites sometimes,
Speaker 2: and I just like, I like topical diseases, particularly if
Speaker 2: they interface with cool bioengineering. And I'd been working on
Speaker 2: the universal vaccine work, and so I started wondering, I'm like,
Speaker 2: you know what, I wonder if that same idea of
Speaker 2: the conserved Achilles heel that's found across all flu or
Speaker 2: all HIV.
Speaker 3: I wonder if snake venom.
Speaker 2: Toxins have that, Because if that's true, maybe you don't
Speaker 2: need to make six hundred and fifty different anti venoms.
Speaker 2: Maybe it's actually that you only make one cocktail of
Speaker 2: broadly neutralizing antibodies and it could work against all snakes.
Speaker 3: A universal anti venom. And so I did a little
Speaker 3: you know, playing around on my computer, and sure enough,
Speaker 3: there's basically like ten major toxins that all snakes use.
Speaker 3: Nature's lazy.
Speaker 2: And then when I pulled up a bunch of sequel
Speaker 2: is from a bunch of different snakes and I compared
Speaker 2: where they buried, where they mutated relative to each other
Speaker 2: versus not again, I found a little conserved spot and
Speaker 2: it's it's the business end, right, because these toxins can mutate,
Speaker 2: except they can't mutate right where they need to go
Speaker 2: bind your neurons, your nicotinic casido colon receptor to paralyze.
Speaker 3: You and so forth.
Speaker 2: And so at that point I got pretty stoked, where
Speaker 2: I was like, I'm pretty sure this is and like
Speaker 2: at the time, no one had been talking about broadly
Speaker 2: neutralizing anybody's outside of viruses.
Speaker 3: And I was like, this is so cool.
Speaker 2: And so then I was like, all right, where do
Speaker 2: I find a person who has been met a couple times?
Speaker 3: Right?
Speaker 2: And I was like looking for a clumsy snake researcher,
Speaker 2: Like there's like a site in Costa Rica. There's a
Speaker 2: place in Arizona. There's some places in India where I
Speaker 2: was reaching out and like I was kind of coming
Speaker 2: up empty, and then I don't know how, somehow, like
Speaker 2: I desperately just started like Google searching, and I found
Speaker 2: these insane articles about this guy named Tim Freedy who
Speaker 2: had spent like at the time, over seventeen years self
Speaker 2: immunizing hundreds of times with sixteen different species of snake.
Speaker 2: What he did is he milked the snakes, he weighed
Speaker 2: out microgram initial doses and administered it, and then he
Speaker 2: escalated over a period of months up until the point
Speaker 2: that he took milligrams. And it was only after he
Speaker 2: built up that immunity. Then he would then have the
Speaker 2: animals challenge.
Speaker 3: Him because no one lives people. You can't live from
Speaker 3: a mamba bid it. He'll kill you. Yet he is
Speaker 3: able to take it. You see that video.
Speaker 2: What you don't see is he spent about nine months
Speaker 2: building up immunity against it by starting with microgram trace doses.
Speaker 1: That's crazy. So you're like, that guy is walking universal
Speaker 1: anti venom.
Speaker 3: Yeah, if anybody has.
Speaker 2: The secrets of universal anti venom, it's pumping through this
Speaker 2: guy's veins right now and so I was like, I
Speaker 2: have to meet him. I couldn't find his contact information
Speaker 2: anywhere online, and so I contacted the reporters and one
Speaker 2: of them put me.
Speaker 3: In touch with them and had his number.
Speaker 2: And so I had this call and I told I
Speaker 2: remember it super clearly, and where I was just like, look,
Speaker 2: I know this may be awkward, but I would love
Speaker 2: to get my hands on some of your blood.
Speaker 3: And his response was I've been waiting for this call
Speaker 3: for a long time.
Speaker 1: And and so what happened, and.
Speaker 2: Then what I do is we just scheduled twenty eight
Speaker 2: days apart two blood draws and each one was for
Speaker 2: twenty mili liters, so that there was no risk as
Speaker 2: to the blood dramaut This is like a couple of tubes.
Speaker 2: And so then that that got sent over to my lab.
Speaker 2: I then processed it in my and I separated out
Speaker 2: the serum and the cells, and from the serum, I
Speaker 2: wanted to check his work. I think, you know a story,
Speaker 2: you know, seemed credible and stuff what I wanted to confirm.
Speaker 2: And so I had ordered a series of snake venoms.
Speaker 3: Which, by the way, it is suspiciously easy to order.
Speaker 2: The bit of mistakes, I have learned during this project.
Speaker 2: I was like, this should not be this easy anyway.
Speaker 2: So I had a bunch of panel of snakes, some
Speaker 2: that he said he'd immunized against, and I also picked
Speaker 2: ones that he never had.
Speaker 1: Oh interesting, this is testing the universality.
Speaker 2: Yeah, yeah, And so I tested his sierra and I
Speaker 2: also tested mine and a couple other control serra on
Speaker 2: this on the venoms. Now, the control people like me
Speaker 2: who have never been bit, we had no response to
Speaker 2: this serum. He had blazingly high responses to all the venoms,
Speaker 2: including the ones he had never been exposed to, including
Speaker 2: new genera like very different snakes.
Speaker 1: So, based on this, right, you come up with this
Speaker 1: anti venom cocktail that seems like it could work against
Speaker 1: not all venomous snakes, but a lot a lot of
Speaker 1: different kinds of venomous snakes. You publish a paper about
Speaker 1: this in the journal Cell. Where does it go from here?
Speaker 1: What happens next?
Speaker 2: We've reached out to the Welcome Trust and so some
Speaker 2: other groups that might be interested in this. We've also
Speaker 2: reached out to I guess I won't say their names,
Speaker 2: but there are some pharmaceutical companies that develop anti venom
Speaker 2: to try to see if this is something they'd be
Speaker 2: interested in doing a partnership on to pick up. I
Speaker 2: think my feeling is that I would ideally like to
Speaker 2: have a pharmaceutical partner to go develop this with or
Speaker 2: a massive support from some foundation, because otherwise it's you
Speaker 2: can make it profitable, you can unfracture that market, and
Speaker 2: you could be manufacturing this and serve maybe a five
Speaker 2: hundred million.
Speaker 3: Dollars per year market.
Speaker 2: But to get there you have to go spend at
Speaker 2: least ten and probably more like twenty million dollars on
Speaker 2: GMP and some other early activities, and then twenty five
Speaker 2: million for clinical and I think it's hard to imagine
Speaker 2: who's going to put that money up front for what
Speaker 2: is a relatively small profit, which is the whole frustrating
Speaker 2: aspect of neglected tropical diseases, and.
Speaker 1: That's why they're neglected. Yeah, we'll be back in a
Speaker 1: minute with the lightning round. Okay, last thing is the
Speaker 1: lightning round. So, as I understand that you dropped out
Speaker 1: of school to run your family in hotel restaurant when
Speaker 1: you were in high school, or you took a year
Speaker 1: off high school, what's one thing you learned from that. Yeah.
Speaker 2: I think one thing I learned is that people on
Speaker 2: teams don't that people do not crave chaos. I think
Speaker 2: people want to know what the people are calmed down
Speaker 2: by knowing that they're rules, even if the rules don't
Speaker 2: benefit them. And I dropped out to go run the restaurant,
Speaker 2: and I was like fifteen year old kid, and you know,
Speaker 2: initially people didn't really listen to me.
Speaker 3: You know, it was just like a crazy time.
Speaker 2: And that was crazy for the employees because the employees
Speaker 2: are like, I don't know, like your son's here, but maybe,
Speaker 2: you know, maybe David's going to die and my dad's
Speaker 2: going to die.
Speaker 3: And then my mom was like, let's just shut it down.
Speaker 3: I can't deal with that. I'm like, Mom, we need
Speaker 3: the money to be able to go pay for the bill,
Speaker 3: the medical bills. You know.
Speaker 2: So everyone was acting chaotic and it was like extremely
Speaker 2: difficult to manage the team and try to keep people
Speaker 2: focused to do their jobs. And you know, this thing
Speaker 2: happened where one evening, one of our cooks was like
Speaker 2: walking out and he had this big bag and I
Speaker 2: went over and I was like, what the hell are
Speaker 2: you doing? And I realized he was stealing a bunch
Speaker 2: of steaks, like it was just stakes, but it was
Speaker 2: with a bunch of the other chefs, and I was
Speaker 2: just like, I didn't do it for a tactical reason.
Speaker 2: I just did it because I was fed, and I'm like,
Speaker 2: you're stealing from my dying father and I just the
Speaker 2: last thing I need. So I was just like, give
Speaker 2: it back, you're fired, go away, And they were shocked
Speaker 2: and I was like, no, no, you're fired. You're not
Speaker 2: allowed to come back in anymore. We'll send you your
Speaker 2: severance basically in two weeks, get.
Speaker 3: The hell out of here.
Speaker 2: And like what I was not anticipating is the next
Speaker 2: day everybody showed up for work and suddenly there was
Speaker 2: actually everyone was calmer, And I think it was the
Speaker 2: transition of perception of power that they were like, they want,
Speaker 2: you know, I did something harsh, and yet suddenly everybody's
Speaker 2: performance improved, partially because they're like, Okay, now I know,
Speaker 2: like the hand that feeds, But it was also like
Speaker 2: knowing that there was some rules and there was a plan. Yeah,
Speaker 2: and I want to leave you with the thought that
Speaker 2: wasn't like my lesson was like okay, be like the
Speaker 2: Red Queen all the time.
Speaker 3: That's not absolutely the way to go. That's not leadership.
Speaker 2: But I think what I did learn is that when
Speaker 2: times are difficult, people prefer to know that there's a
Speaker 2: plan and it's organized and there's a solution, even if
Speaker 2: it's rules that don't benefit them, rather than having opened
Speaker 2: into chaos. And I think that was counterintuitive to me
Speaker 2: because my personality is different actually thrive in chaos and
Speaker 2: having those sorts of complicated choices and I resent confinement
Speaker 2: of any form. But I think that that actually for
Speaker 2: most organizations, that's empowering and important. And to articulate the
Speaker 2: rules and people know there's a system that people are like,
Speaker 2: I feel comfortable because now I understand and it can
Speaker 2: work in a predictable environment.
Speaker 3: And I think that part's important.
Speaker 1: So that's something you learned running the restaurant that has
Speaker 1: helped you as a CEO. I know you recently bought
Speaker 1: the restaurant, so now you're a restaurant owner. Is there
Speaker 1: something you've learned running a biotech company that now helps
Speaker 1: you running a restaurant?
Speaker 3: Oh so yeah, yeah.
Speaker 2: Well externalizing responsibilities so I don't run the restaurant. I
Speaker 2: bought the hotel and restore or the restaurant and some
Speaker 2: of the properties, not the full hotel. Some other people
Speaker 2: bought some of the bungalows. And then what I did
Speaker 2: is I basically wanted to maintain the value of the
Speaker 2: property and increase it and make sure that all the
Speaker 2: people who some of us have worked for our family
Speaker 2: since my childhood, that their jobs weren't compromised, which during
Speaker 2: the pandemic.
Speaker 3: Where tourism was like really bad, like there was a
Speaker 3: risk of that.
Speaker 2: And so I run it essentially as a it's a cooperative.
Speaker 2: It's really like, I don't extract financing from it. I
Speaker 2: have basically a guy we worked with for a long
Speaker 2: time and another team member. I've just told them, like, look,
Speaker 2: my objective is for you to maintain the reputation of
Speaker 2: the place. Just keep running it well and make sure
Speaker 2: I don't. And my one requirement is I need to
Speaker 2: not think about it at all.
Speaker 1: Huh.
Speaker 2: And I'm working on the universal vaccine techt so maybe i'll,
Speaker 2: you know, in the future, I'll want to go and
Speaker 2: settle around and be a restaurant tour but like right now,
Speaker 2: I just needed to not think about it.
Speaker 1: Her to use the word hard ass a few times
Speaker 1: in other interviews, are you a hard ass?
Speaker 2: I think on myself and on an expectation of detailed
Speaker 2: I think research needs to be done in a very
Speaker 2: particular process. I don't think my team would say I'm
Speaker 2: a hard ass.
Speaker 3: I don't I think that, or maybe I've evolved over time.
Speaker 2: I think I have exacting standards of expectation of how
Speaker 2: to get things done. But it's not like it's more
Speaker 2: like me driven of anxiety than me going in.
Speaker 3: And like I don't bark at people or anything. I'm like, guys, we.
Speaker 1: Have to have this anxious hard as.
Speaker 2: Yeah, I have to be like, look, we have to
Speaker 2: have a set of standard you know, controls, and then
Speaker 2: we need to run this in a certain way and
Speaker 2: we need to have things documented. Otherwise we're just walking
Speaker 2: on quicksand and we'll just mess up every time. So
Speaker 2: now I don't think I'm a hard ass. I think
Speaker 2: there's certain things where I have exacting expectations. But I
Speaker 2: also think that you have to have that if you
Speaker 2: want to build a I've struggled to find an example
Speaker 2: of a big company that was built on technology where
Speaker 2: the CEO did not have that property. Because I think
Speaker 2: there's a certain expectation of excellence that is required to
Speaker 2: build something great. Maybe a little bit of a hard ass,
Speaker 2: A little bit of hard ass, all right, occasional.
Speaker 1: Jacob Glanville is the founder and CEO of Centovax. You
Speaker 1: can email us at problem at pushkin dot fm, and
Speaker 1: please do email us. I read all the emails. Today's
Speaker 1: show was produced by Gabriel Hunter Chang, edited by Alexandra Garriton,
Speaker 1: and engineered by Sarah Bruguer. I'm Jacob Goldstein, and we'll
Speaker 1: be back next week with another episode of What's Your
Speaker 1: Problem