AI transcript
0:00:25 I love vaccines. I really do. Vaccines train your body to make these antibodies that protect
0:00:31 you against deadly diseases. It’s a thing you get so you don’t get sick in the first place.
0:00:38 And it’s so clever and so elegant and so obviously useful. I think it is honestly fair
0:00:43 to say that vaccines are truly one of the greatest inventions of all time on the very
0:00:48 short list. They’ve saved hundreds of millions of lives. Give me all of them. Give me all
0:00:59 of the vaccines. But I got to say, the flu vaccine sucks. The flu vaccine sucks. It really
0:01:07 does. And for a somewhat simple reason. The flu virus mutates so quickly that we can’t come
0:01:13 up with vaccines fast enough to keep up with it. So every year, scientists develop a new
0:01:20 vaccine. But even in the time it takes to manufacture that vaccine, the virus keeps mutating. As
0:01:24 a result, even if you get a flu shot every year, there’s still a good chance that you’ll get
0:01:32 a bad case of the flu. Last year’s flu shot, for example, was only about 35% effective. And
0:01:38 so for decades now, scientists have asked a fairly obvious question. Is there some way to come
0:01:43 up with a flu vaccine that would work not just for the strain of flu that is circulating right
0:01:48 now, but for almost all strains of flu, including strains that haven’t even evolved yet?
0:01:58 I’m Jacob Goldstein, and this is What’s Your Problem, the show where I talk to people who
0:02:04 are trying to make technological progress. My guest today is Jacob Glanville. He’s a bioengineer
0:02:10 and an immunologist. And he’s the founder and CEO of Centivax, a company that’s trying
0:02:17 to make a universal flu vaccine, a flu vaccine that will consistently and reliably prevent people
0:02:18 from getting the flu.
0:02:23 You imagine talking to a generation that didn’t have flu anymore. They would think we were nuts.
0:02:26 They were just like, oh, yeah, every year we have a circulating pandemic. And then six months
0:02:30 later, there’s another one. And yeah, you know, 50,000 people die. But what do you do? And
0:02:34 like, that’s nuts. But we take it for granted.
0:02:40 The vaccine that Jacob’s company, Centivax, is developing for flu is likely to go into human
0:02:47 trials next year. The company is also in earlier stages of developing universal vaccines for HIV
0:02:55 and COVID, among other diseases. And wild card, they have also worked on creating a broadly effective
0:03:00 anti-venom for snake bites. We talk about snake bites later in the conversation.
0:03:06 To start, Jacob told me about the moment he first got the idea for a universal vaccine.
0:03:13 It was around 2012. He was working for the drug company Pfizer. And he wasn’t working on vaccines,
0:03:19 but he was doing something related. His job was to identify antibodies that could be used to treat
0:03:25 disease. And at this particular moment, he was studying antibodies that would bind to a particular
0:03:32 protein called PCSK9. And so I was riding back on my motorcycle one evening, and I was reflecting on
0:03:38 this problem where there’s this target called PCSK9. It kind of looks like Mickey Mouse’s head.
0:03:45 And they were really wanted antibodies against kind of where the neck is. If you get an antibody there,
0:03:50 then that can affect cholesterol and lower cholesterol. The problem is that they’re getting
0:03:54 antibodies against the ears, and they weren’t getting antibodies against the neck. And so I was
0:03:59 trying to figure out, is there an engineering way to sort of focus the immune system at arbitrary
0:04:05 sites? That would save me a bunch of time. And I started imagining, what if I were to take
0:04:13 that target, not just from humans, but from like a donkey and an alligator and a chicken and like,
0:04:18 just take a swath of different versions of that. They were different just about everywhere up in the
0:04:24 ears, but they were the same down where the neck was. And then if I mix those together and I diluted
0:04:30 each one, there wasn’t enough of any one of the species of PCSK9, then maybe only the neck would be the
0:04:34 thing which was shared across all of them and the entire immune system would focus on that.
0:04:40 So like in total, the sort of sum total of the mix, it would be like a lot of neck. The neck is
0:04:46 conserved. The neck is what is the same. And there’s only enough of that to induce the antibody
0:04:51 response. So that then if you, whatever, inject that into an animal or a person, what the person’s
0:04:53 immune system is going to see is a lot of neck.
0:04:57 Yeah. And so they finally focus on the neck instead of getting distracted by the ears.
0:05:02 That was the principle. And so I got home and then at a certain point I realized I was being an idiot.
0:05:07 And what this was, was not a way to save a few months on an antibody discovery campaign,
0:05:12 that this was a potential window opening to the, to all the Holy grail of vaccine science.
0:05:20 The Holy grail is that all of the major viruses that we’re confronted with flu influenza, HIV, Ebola,
0:05:27 these viruses mutate and change, but they always have some little spot that they cannot mutate.
0:05:31 And those spots are always super important. That’s why they can’t mutate it. Because if you
0:05:36 mutate it, the virus is no longer infectious. And normally they get away with it by having
0:05:41 distracting areas and most of the surface that can mutate. And that’s why we have to update our
0:05:42 flu shots every year.
0:05:46 Distracting meaning distracting to our immune systems, like our immune system is like,
0:05:51 oh, I like the, I like the ears. I like that shiny part on top. And that’s the part that keeps changing.
0:05:55 Yeah, yeah, yeah. Basically the conserved Achilles heel is a small site and most of the
0:06:00 surface can vary and it can’t, it gets away with not changing the critical site by varying lots of
0:06:04 stuff around it and taking advantage of the fact that the immune system doesn’t know the difference.
0:06:10 And so the ability to focus the immune system against a conserved site would be the basis of
0:06:16 a universal vaccine. Because instead of targeting one strain of flu or one strain of coronavirus or
0:06:21 one strain of HIV, you could target the shared sites that the virus is never allowed to mutate.
0:06:25 And if you do that, then you’re suddenly hitting the entire class of influenza viruses,
0:06:27 including future ones that haven’t evolved yet.
0:06:32 Right. I mean, that part of the idea is the part everybody knew already, right? Like that is the
0:06:37 relatively obvious idea. It’s like, don’t go for the part that changes. Go for the part that’s the
0:06:44 same, right? The hard thing is how do you do that? So, so had, when you describe the idea of like,
0:06:50 oh, just take a bunch of different ones, dilute them, mix them together. Nobody had thought of that
0:06:58 before? Yeah. So surprisingly not. To your point, people, since the nineties were aware of these
0:07:02 conserved sites. And so they knew where the sites were. We had crystal structures.
0:07:05 It was just, how the hell do you get the immune system to focus on those sites was the problem.
0:07:09 Yeah. And people had tried a couple of different things. They tried chopping out parts of the
0:07:14 protein, but then, then the site you’re interested in falls apart. It’s like trying to grab a snowflake.
0:07:19 It’ll melt in your hands. They tried a couple of other techniques that didn’t work out.
0:07:24 So, okay. So you have this new idea for how to make a universal vaccine that nobody’s tried before,
0:07:30 which to use flu for an example would mean you take a bunch of different strains of flu. And in
0:07:36 particular, the sort of spike protein of the, of the flu that your immune system sees, then you dilute
0:07:42 them and mix them all together in a single vaccine. So what the patient’s immune system winds up seeing the
0:07:48 most of is the part that’s the same in all those different strains, the part that doesn’t change.
0:07:55 And then ideally the patient will develop antibodies to that part, the part that doesn’t change.
0:07:59 And therefore the patient will be immune to like almost any strain of flu.
0:08:03 Yeah. And you recognize it might not work, right? You always are like, look, this is a pipe drain,
0:08:07 but like I could not go to sleep because I was like, if this works, this is such a stunning breakthrough
0:08:12 that it’s like, it’s hard to sleep when you’re thinking about that. It sort of becomes all consuming.
0:08:20 So you get this idea and you’re working for Pfizer, a company that makes vaccines, by the way.
0:08:21 What do you do?
0:08:26 Yeah. So again, I was not doing anything involving their vaccine group.
0:08:28 I was doing important for intellectual property reasons.
0:08:31 Yeah. I was not working on vaccines at Pfizer.
0:08:40 I, I, I resigned. So I did two things. I started, uh, my first company distributed bio, and I also applied
0:08:43 for the PhD program in immunology at Stanford.
0:08:46 And you do this because of your idea?
0:08:51 Yeah. Yeah. Because basically I applied to the PhD program because I was like,
0:08:56 if I’m wrong, I need to stop thinking about this. I need to surround myself with brilliant
0:09:00 immunologists who can kick holes in this. And, and I need to be able to make sure I’m not being
0:09:06 myopic. And because, and then if I’m right, I need the world to hear me. And so I need to be a card
0:09:11 carrying PhD immunologist from Stanford. So that people go, okay, this, this guy isn’t just some
0:09:11 Yahoo. Yeah.
0:09:18 Um, and then for the company side, I just saw this opportunity to be able to go test it because I,
0:09:23 originally I, I did go out and I tried to talk to some VCs and, and 2012. And I think they’re,
0:09:26 you know, predictably their answer is like, what the hell is this? And who the hell are you?
0:09:31 And you had a bachelor’s degree, right? And you’d worked at Pfizer for a couple of years,
0:09:35 like a million other people. So, so not, you know, you can’t blame them. I was like,
0:09:40 I guess I’m nobody right now. Let me go fix that. Yeah. And, uh, and so I, I decided that
0:09:45 I was going to go found a company because there was some, there was some work I was doing at Pfizer
0:09:49 that I’d published, created some publications on using the deep genomic sequencers to look at the
0:09:53 immune system and then building better antibody libraries with what we learned about that.
0:09:57 And I realized there was a business that could be built on that. And my intention was to build
0:10:02 that business and use it to subsidize some of the early proof, uh, de-risking experiments on this
0:10:07 universal vaccine concept. And, and so that’s what I did. So I just did both for five years and didn’t
0:10:12 sleep that much. And until the PhD graduated from that. And then later I sold the first company
0:10:16 distributed bio. So the company you start, you’re selling your, your clients are drug companies,
0:10:21 essentially. Right. But you’re doing that. That’s sort of your side hustle. That’s sort of funding
0:10:30 your, your vaccine dream. Right. And while you’re doing that, you start doing this research on your
0:10:37 vaccine in pigs in Guatemala. Right. Yep. Tell me about that. Um, the background is I grew up in
0:10:43 Guatemala. My parents are Americans, but they met in Guatemala in the seventies and they built this hotel
0:10:49 restaurant with my grandmother. Hippie dream. Yeah. The hippie dream. That’s exactly what it is.
0:10:53 There’s, there’s small hippie enclaves down there. And then there’s most of the village is
0:10:57 Zutawil Mayan. And then there’s Cachiquels and some other Mayan communities. And it’s, it’s very
0:11:02 beautiful lake. So it makes sense that the hippies would go there. Yeah. Uh, the civil war largely drove
0:11:07 them away, but my family, when I was a little boy, they went down there to try to fix up and sell the
0:11:12 property. And then one thing led to another and we ended up becoming innkeepers. And so I grew up in,
0:11:18 in the village. Um, I think it probably had an effect on my interest in immunology in the first
0:11:22 place. Uh, and, and I had this connection to Guatemala and I ended up maintaining a connection
0:11:29 to USAC, which is the university of San Carlos, the national university. And so fast forward in my
0:11:35 career too, when I was thinking about universal vaccines, like one of my, I say one of my deep
0:11:40 impressions left from some work at Pfizer was this, I was very impressed with a group that was
0:11:45 doing animal health work because I felt like instead of using mice, they would often ask what’s the most
0:11:51 relevant and similar animal model to humans for this indication. Mouse is not a person like no animal
0:11:56 is a person, but you can find something that’s a closer fit and, and waste less time on failed
0:12:00 translation. Yeah. And so I liked, I had this technology. I was trying to figure out where to
0:12:06 apply it. I actually called one of the guys and I was like, what’s the veterinary market that has
0:12:12 rapidly mutating pathogen. That’s also found in humans. And he said, it’s definitely flu and pigs.
0:12:17 They get the flu. In fact, they transmit it to humans. And so things are definitely not as convenient
0:12:21 as mice, but I felt that the data would be much more meaningful because they actually get the flu.
0:12:29 So I ended up doing it back in Guatemala with Erwin Calgua, my collaborator at the University of San
0:12:34 Carlos, and some property that my father had. So I ended up making some calls. I found out we could
0:12:40 get the pigs. There was a vet who was involved in the H1N1 2009 pandemic shift monitoring.
0:12:44 You’re doing it in Guatemala because it’s cheaper, basically? You’re offshoring your research?
0:12:49 Yeah. It’s way cheaper. Yeah. Radically cheaper and faster. I think the cycle time is astonishingly
0:12:54 slow to do animal studies and ask for grants. You’re lucky to get a study done once every two and a half
0:13:00 years, according to the US model. Whereas in Guatemala, the costs were radically cheaper. I could
0:13:06 build a facility to spec. And I’m an engineer, so I need to be able to do cycles. And so this enabled me.
0:13:10 I think we ran five studies there over a couple of year period. We were able to go pretty quickly,
0:13:16 go in and rapidly de-risk this universal vaccine technology in a way that was economically feasible,
0:13:21 given the growing profits, but still finite profits that I had from the antibody discovery
0:13:22 and software side of the business.
0:13:28 So when you’re doing those pig studies, I mean, just to return to your initial idea of
0:13:34 using essentially different strains, let’s say, you got to figure out what’s the right concentration.
0:13:40 Because if you do too little, you don’t get any meaningful immune response. And if you do too much,
0:13:44 then you’re getting immune response to the parts that are not conserved, to the parts that you don’t
0:13:45 want immune response to.
0:13:49 Exactly. I was also just proving the concept, right? Because I think there’s definitely people
0:13:54 who are like, this isn’t going to work. There’s no way. And look, if I’m wrong, then it doesn’t
0:13:58 matter if I put 15 things in. If each one’s below the dose and they’re not interacting like I was
0:14:03 hypothesizing, then you should see no immune response, right? So I could have just been wrong.
0:14:06 That’s the other thing. I was testing to see, does the principle hold? And the answer was
0:14:07 definitively yes.
0:14:13 So, okay. So you have this idea that it works. Somewhere around here, you sell, I don’t know
0:14:17 which one is the side hustle and which one is the main hustle. I guess vaccinating pigs in
0:14:21 Guatemala sounds like a side hustle, even though it’s the thing you really care about, right?
0:14:32 You sell distributed bio and you spin out, sent to VAX, the vaccine company, right? And then what?
0:14:33 Then where are you?
0:14:42 Yeah. So it was a good time. So we got, the Gates Foundation had awarded us this, in the pandemic
0:14:47 threat grand challenge award to test the vaccine, no longer in Guatemala, but up in American facilities
0:14:52 that had biosafety containment so that we could challenge the animals who’d been vaccinated
0:14:58 with these strains that had evolved after the mixture. So we deliberately pretended it was 2007
0:15:04 and only included strains up to 2007. Then we challenged the animals with the 2009 pandemic
0:15:07 shift virus, a 2012, a 2017 virus.
0:15:11 That’s a big question, right? It’s like testing something that’s out of the model, right?
0:15:17 Like it’s saying, okay, we give somebody this vaccine and then there’s a new kind of flu.
0:15:18 Does it work?
0:15:19 Yeah.
0:15:19 Yeah.
0:15:23 And it felt that that was essential, which by the way, those same pigs, we pulled their serum
0:15:27 out of the freezer over the last couple of months and they neutralized the H5N1 that’s currently
0:15:30 outbreaking in cows and chickens and some people.
0:15:30 Uh-huh.
0:15:31 The bird flu.
0:15:32 The bird flu everybody’s scared of.
0:15:33 Yeah, it creates super broad immune response.
0:15:34 Yeah.
0:15:42 So the timing was good. CRL wanted to buy. I was happy to do it. And, uh, my condition
0:15:46 was, I’m like, look, I want to take this universal vaccine technology, uh, with me to a new company.
0:15:53 And they agreed to that. That was December 31st, 2020 is when the, when the sale completed.
0:15:54 And so basically January 1st.
0:16:00 That is a remarkable time to go all in on a universal vaccine, December 31st, 2020.
0:16:07 So we transitioned over January 1st, 2021. Uh, I am now the CEO and founder of Cinevacs. And I,
0:16:11 I started calling an army of geniuses of the best people that I’ve worked with to gather together.
0:16:13 And I was like, look, this is going to be the big one where.
0:16:17 It’s like a, like a heist movie, like Ocean’s 11 or something.
0:16:21 Yeah. It was like the best people of my entire career I worked with. You don’t need a lot. You
0:16:25 just need every person to be exceptional. And like, if we do our jobs, right, we touched the long
0:16:25 arc of history.
0:16:30 Yeah. So, so what have you figured out? Like what have been the
0:16:33 key things you’ve figured out since then?
0:16:39 We identified, uh, a couple extra people we brought in, including Jerry Sadoff. He’s this
0:16:47 guy who’s has more vaccines approved than anyone alive. So things like Gardasil, MMRV that all
0:16:52 children take, you have the coronavirus vaccine from, from J and J the one shot. And, you know,
0:16:56 I think 14 vaccines have been approved under his watch. It wasn’t just that he had done a huge
0:17:01 amount of like the modern vaccines that define the modern health era. It’s that his hit rate
0:17:06 was unusually high. Like it wasn’t like he worked on a hundred to get to those 14. He had like his
0:17:11 rate ratio of success was unusually high. And that told me I wanted to work with them. And so I
0:17:15 called him up and went out to have dinner with them. And I was like, Jerry, you told me this
0:17:19 universal vaccine technology is the only thing you thought was worth a damn. Like, come, come join me
0:17:23 and like, let’s kick a hole in the universe. And so he came. And the reason I’m telling you this is
0:17:28 that he, he didn’t just come in with phenomenal clinical plans, which he did. Uh, he also came
0:17:31 in with some strategies where he’s like, one of the things I’ve noticed for both the coronavirus
0:17:37 vaccines and the RSV vaccines was that the folks who added in little mutations to keep those spikes
0:17:42 stable, those vaccines were successful. And the folks who didn’t add in good stabilizing mutations,
0:17:47 their vaccines were unsuccessful. Huh? And he said, I think that that’s just a critical thing.
0:17:52 You want to trap these spikes in their stable form so the immune system can target what the
0:17:56 spike looks like before it attacks a cell or before it falls apart to confuse the immune system.
0:18:01 So just to be clear, like the, the spike proteins, it’s the, the hemagglutinins that,
0:18:07 that are in nature on the outside of the, of the, of the flu virus, they have a three-dimensional
0:18:12 shape, right? Yeah. They can change three-dimensional shape. And that actually turns out to be important
0:18:16 for sort of simple mechanical, like a key fitting into a lock reason.
0:18:22 Right. And it’s, and they don’t, if you rip them off the virus as you are, when you’re presenting
0:18:25 them in this vaccine, necessarily stay in the shape you want them to stay in. That’s a problem.
0:18:30 Yeah. They’re kind of like a little three-pronged grappling hook and they change shape in order
0:18:34 to like hook into the cell membrane and then tear it open. And they’re designed kind of like with
0:18:38 hinges because they need to be able to be mobile and make changes. And so this protein is not inherently
0:18:43 stable, but what you want is you want the thing very stable because you want the immune system to train
0:18:49 on defeating the trimer when it’s in, it’s sort of cocked, cocked and loaded, but prior to shoot
0:18:54 position. Yeah. And, and we’ve seen with RSV and coronavirus that that was absolutely essential
0:18:58 for the successful vaccines. Right. And so anyway, Jerry came in and was like, we should do this with
0:19:03 flu. I had a bunch of experience stabilizing proteins from work. We did stabilizing antibodies
0:19:10 at Pfizer and then also at my company, my distributed bio. And so we ran a quick campaign and we identified
0:19:15 these great stabilizing mutations and they had like a pretty stunning effect on the quality of the
0:19:21 immune response. So you’re doing this basically atomic level engineering of the proteins, right?
0:19:22 Yep. That’s a thing. Go on. What else?
0:19:27 And then the other thing, the major thing we’ve done is we started the manufacturing. We advanced the
0:19:32 program, not just for flu, but we’re also, we have data validating the universal coronavirus
0:19:40 vaccine. We’re testing on HIV. We’re testing on malaria and a number of other pathogens right now
0:19:44 to be able to create a portfolio. So those have been some of the major activities in the last couple of
0:19:50 years. When are you doing human clinical trials? Yeah. So we’ve got about nine months left of
0:19:55 manufacturing or eight months of manufacturing. And then you, you spend a month getting permission
0:20:01 from the FDA to start your, your study. And then we’d start human trials. So, okay. So next year
0:20:05 you’re starting human trials next year. So, so when you think about the future, the future of the company
0:20:08 of your work, like what, what are you worried about?
0:20:14 So I worry about less and less things. And then the things I worry about evolve. So in terms of,
0:20:21 is it going to be safe? I worry about that extremely little. Um, we have been vaccinated with
0:20:28 influenza, HA protein since the 1940s. It’s actually the best validated diverse class of versions of HA
0:20:32 compared to any other vaccine that’s been tested. And it’s the tolerance, the history of safety has been
0:20:39 extremely good. We’re using the, um, Pfizer biointech MRNA chemistry. So you can get a
0:20:44 non-exclusive license to it. That’s the same one they used for the COVID vaccine. Yeah. So it’s been
0:20:49 in billions of people. So we know what the safety profile is. So safety, I’m not concerned about in
0:20:54 terms of efficacy, like how well it works. Uh, I basically don’t believe in any one animal’s immune
0:20:59 system because you could always overfit. The immune system could overfit in a certain bizarre and
0:21:07 unpredictable way. And so we’ve tested this in pigs, but also ferrets, also rats, also mice, also cows,
0:21:13 and also human immune organoids, which is organ donors offer their lymph nodes. They’re smushed up and
0:21:16 you basically create a bunch of little mini lymph nodes from a donor and you can vaccinate them under
0:21:22 different conditions to see how someone with a lifetime of immune memory, including to flu and vaccines
0:21:28 would respond to our vaccine or a control vaccine. And when we did that, as well as all the other
0:21:34 animals, we consistently saw this universality effect. And so going into the human trials,
0:21:40 I think we’re pretty bullish that the effect is going to be dramatically better than, uh, the
0:21:45 current vaccine. So I think we’re going in assuming that the human trials probably will perform well,
0:21:49 but I want to say I won’t sleep well at night until I get that data. And I’m like, okay, yeah,
0:21:54 we’re, we’re, we’re on solid footing. I, I, we’ve done everything I can to de-risk it with these
0:21:58 other organisms and, and even human immune organoids. And now it’s time to run it in humans.
0:22:04 Um, fundraising is always a headache where we’ve got now at least multiple groups gathering around
0:22:08 with term sheet options and we’re looking at them, but it’s, uh, it’s been, I would just to put it
0:22:12 lightly, a difficult period for biotech fundraising that we’ve managed to survive where a number of
0:22:17 other companies have not. But, uh, you know, I’m, I’m probably gained some gray hair and probably,
0:22:20 uh, you know, took away some of my health span as a consequence of surviving this period.
0:22:25 Uh, I mean, does that last thing mean you’re afraid of running out of money?
0:22:30 That’s what, I mean, every company worries about that. That’s the nature of venture. We’ve managed
0:22:35 to pull it together and we just got this grant, which covers us. But the, the, the fear is that
0:22:39 we’re stuck, that we, we need to go continue raising money so that we can go pay for the rest of
0:22:45 manufacturing and pay for clinical and, and, and arm for the next parts. And, and to be blunt,
0:22:50 this has been an absolutely terrible period in biotech. So we got 75% off on all of our equipment
0:22:54 for my entire laboratory. Cause we got it from auctions. A lot of the stuff was in like new stuff
0:23:00 in boxes where a company just ran out of money and they’re stuck. And I benefited from it. I’ve
0:23:05 benefited from being able to hire remarkable people that otherwise were struggling to find an opportunity
0:23:10 because of it’s, we’ve basically lived in this, like a little bit of a biotech hangover after I think
0:23:15 there was too much investment and sometimes it’s some pretty goofy stuff during the pandemic for biotech.
0:23:19 And I think we’re in this like a little bit of a headache, a little bit of a macro economic global
0:23:23 uncertainty area. And those things have both slammed up against biotech in an unproductive way.
0:23:30 Yeah. Um, so, okay. What’s the happy version of the story?
0:23:37 The happy version is that our vaccine works the same as it has in all those animals and organoids
0:23:43 that we’ve seen. We bring it forward. Universal vaccine just becomes the vaccine because that’s
0:23:48 suddenly a vaccine that you take and you don’t get sick. The first thing it does is it creates
0:23:54 a massive improvement in global health. And then the major impact of, you know, flu kills people,
0:23:59 right? It gets a lot of people sick. People lose a lot of time from school, pregnant women in their
0:24:04 second trimester to get flu or seven times more likely to have a child with, with schizophrenia and
0:24:10 their adult, like it has, there’s a bunch of like squali and consequences. But the biggest effect is that
0:24:13 when this gets out there, the pandemic era is over.
0:24:18 Uh-huh. And when you say pandemic, you mean flu pandemic, but yeah, the flu pandemics are over.
0:24:23 Yeah. Which is our most common source of pandemics. We had five in the last hundred years. We had,
0:24:28 you know, two or three per century before then. So they got faster. Yeah. We have a lot more people.
0:24:34 We have these pig mega farms. Like we need to fix this. And with this vaccine, you no longer have a
0:24:39 pandemic era because you have a decent proportion of the population that’s already immune to the new
0:24:44 virus strains before they hit. And that’s what the new world looks like. And so that’s the happy version
0:24:50 for flu. But our intention is to do that for every pandemic pathogen, to just one by one go and end the
0:24:55 pandemic era, to come up with countermeasures that first protect the world from pandemics, the medical,
0:25:01 personal and economic costs. Second, protect the world from just major outbreaks. And then ultimately,
0:25:06 I want to have these same tools can arm future decades to attempt eradication campaigns that
0:25:14 previously were not possible. And that’s the future we want to go. We’ll be back in just a minute.
0:25:31 Um, let’s talk about snake bites. All right, let’s do it. Um, how’d you get into the snake bite
0:25:41 business? Yeah. So it was 2017. And I think it was because the world health organization was
0:25:48 announcing, you know, the neglected tropical disease nature of snake bite, kind of declaring it a
0:25:53 neglected tropical disease. Basically saying hundreds of thousands of people are killed or
0:25:58 very badly wounded every year by snake bites. It’s not just some weird thing.
0:26:03 And not enough people are trying to develop countermeasures. And I think what had happened…
0:26:07 Because most of the people who are, who die or are severely injured are super poor.
0:26:15 Yeah. Yeah. That’s, uh, it reminds me of, uh, Monty Python, where they have the Roman Senate and
0:26:19 someone goes, what do we do about the poor? And then all in unison, they put up their hands and
0:26:20 they’re like, fuck the poor. All right, next.
0:26:24 That’s the neglected tropical disease story.
0:26:31 The fundamental problem. Yeah. I think also that, I mean, like, to be fair, I don’t want to be fair,
0:26:36 but like the companies that make anti-venom, most of them are kind of doing it as a public service as
0:26:40 a loss because most of the people who need anti-venom of the millions of bites per year,
0:26:44 they’re, they’re poor. They’re subsistence agriculturalists and their children and people
0:26:50 who live in rural environments. Um, and if you take that market, which is probably like five to
0:26:55 600 million total per year, but it’s fractured across 30 to 40 products. Each of those things
0:27:00 is pretty unattractive. Just to be clear, because you need different anti-venom for different snakes
0:27:04 for different kinds of things. Yeah. There currently is no universal anti-venom on the market. And so
0:27:08 people had started ending programs to make certain types of anti-venoms. And I think that was happening
0:27:14 in 2016. So then in 2017, the World Health Organization brings some attention to this. And then I, you know,
0:27:19 I started thinking about it. I, you know, in my village, we had snake bites sometimes and I just
0:27:23 like, I like topical diseases, particularly if they interface with cool bioengineering
0:27:29 and I’d been working on the universal vaccine work. And so I started wondering, I’m like, you know what?
0:27:34 I wonder if that same idea of their conserved Achilles heel that’s found across all flu
0:27:41 or all HIV. I wonder if snake venom toxins have that, because if that’s true, maybe you don’t need
0:27:48 to make 650 different anti-venoms. Maybe it’s actually that you only make one cocktail of broadly
0:27:51 neutralizing antibodies and it could work against all snakes, a universal anti-venom.
0:27:58 And so I did a little, you know, playing around on my computer. And sure enough, there’s basically
0:28:04 like 10 major toxins that all snakes use. Nature’s lazy. And then when I pulled up a bunch of sequences
0:28:09 from a bunch of different snakes and I compared where they varied, where they mutated relative to
0:28:14 each other versus not, again, I found a little conserved spot and it’s the, it’s the business end,
0:28:18 right? Cause these toxins can mutate except they can’t mutate right where they need to go bind your,
0:28:23 your neurons, your nicotinic acetylcholine receptor to paralyze you and so forth.
0:28:27 And so at that point I got pretty stoked where I was like, I’m pretty sure this is, and like at the
0:28:31 time no one had been talking about broadly neutralizing antibodies outside of viruses.
0:28:35 And I was like, this is so cool. And so then I was like, all right, where do I find a person
0:28:40 who, uh, has been bent a couple of times? Right. And I was like looking for a clumsy snake researcher.
0:28:46 Like there’s like a site in, uh, Costa Rica. There’s a place in Arizona. There’s some places
0:28:51 in India where I was reaching out and like, I was kind of coming up empty. And then I don’t know
0:28:56 how, somehow like I desperately just started like Google searching. And, uh, and I found these insane
0:29:03 articles about this guy named Tim Freedy who had spent like at the time over 17 years, self immunizing
0:29:10 hundreds of times with 16 different species of snake. What he did is he milked the snakes. He weighed
0:29:15 out microgram initial doses and administered it. And then he dose escalated over a period of months up
0:29:19 until the point that he took milligrams. And it was only after he built up that immunity, then he would
0:29:25 then have the animal, the animals challenge him. Cause like no one lives people, you can’t live from a
0:29:29 mamba bite and he’ll kill you. And yet he is able to take it. You see that video. What you don’t see
0:29:33 is he spent about nine months building up immunity against it by starting with microgram trace doses.
0:29:39 That’s crazy. So you’re like, that guy is, is the walking universal antivenom.
0:29:44 Yeah. If anybody has the secrets of universal antivenom, it’s pumping through this guy’s veins
0:29:49 right now. And so I was like, I have to meet him. I couldn’t find his contact information anywhere
0:29:53 online. And so I contacted the reporters and one of them put me in touch with them and had his number.
0:29:57 And so I had this call and I told, I remember it super clearly. And where I was just like, look,
0:30:02 I know this may be awkward, but I would love to get my hands on some of your blood.
0:30:06 And his response was, uh, I’ve been waiting for this call for a long time.
0:30:10 And, and so what happened?
0:30:16 And then what I do is we just scheduled a 28 days apart, two blood draws and each one was for 20
0:30:20 milliliters. So there was no risk as to the, the blood draw amount. This is like a couple tubes.
0:30:28 Um, and so then that, that got sent over to my lab. I then processed it in my, and I separated out the
0:30:32 serum and the cells and from the serum, I wanted to check his work. I think, you know, a story,
0:30:36 you know, seemed credible and stuff, but I wanted to confirm. And so I’d ordered a series of snake
0:30:41 venoms, which by the way, it is suspiciously easy to order the venom of venomous snakes.
0:30:47 I have learned during this project. Um, I was like, this should not be this easy anyway. So I,
0:30:51 I had a bunch of panel of snakes, some that he said he had immunized against. And I also picked ones that
0:30:52 he never had.
0:30:55 Oh, interesting. This is testing the universality.
0:30:59 Yeah. Yeah. And so I tested his sera and I also tested mine and a couple other control sera on this,
0:31:05 on the, the venoms. Now the control people like me who’ve have never been bit, we had no response
0:31:10 to the serum. He had blazingly high responses to all the venoms, including the ones he had never been
0:31:12 exposed to, including new genera, like very different snakes.
0:31:19 So based on this, right, you come up with this anti-venom cocktail that, uh, that seems like
0:31:25 it could work against not all venomous snakes, but a lot, a lot of different kinds of venomous snakes.
0:31:30 Um, you publish a paper about this in the journal sell. Where does it go from here? What happens next?
0:31:35 Um, we’ve reached out to the welcome trust and to some other groups that might be interested in this.
0:31:39 We’ve also reached out to, I guess I won’t say their names, but there’s some pharmaceutical
0:31:44 companies that develop anti-venom to try to see if this is something they’d be interested in doing a
0:31:49 partnership on to pick up. I think my feeling is that I would ideally like to have a pharmaceutical
0:31:55 partner to go develop this with, um, or a massive support from some foundation because otherwise it’s,
0:32:01 you can make it profitable. You can unfracture that market and you could be manufacturing this and serve
0:32:09 maybe a $500 million per year market. But to get there, you have to go spend at least 10 and probably
0:32:14 more like $20 million on GMP and some other early activities and then 25 million for clinical.
0:32:19 And I think it’s hard to imagine who’s going to put that money up front for what is a relatively small
0:32:23 profit, which is the whole frustrating aspect of neglected tropical diseases.
0:32:25 That’s why they’re neglected. Yeah.
0:32:30 We’ll be back in a minute with the lightning round.
0:32:50 Okay. Last thing is a lightning round. Um, so as I understand that you dropped out of school to run
0:32:56 your family in hotel restaurant when you were in high school or you took a year off high school,
0:32:59 what’s one thing you learned from that?
0:33:03 Yeah. I think one thing I learned is that people on teams don’t,
0:33:10 that people do not crave chaos. I think people want to know what the people are calmed down by
0:33:15 knowing that their rules, even if the rules don’t benefit them. And I dropped out to go run the
0:33:19 restaurant and I was like 15 year old kid. Uh, and you know, initially people didn’t really listen
0:33:24 to me, you know, it was just like a crazy time. And that was crazy for the employees. Cause the
0:33:29 employees are like, I don’t know, like your son’s here, but maybe, uh, you know, maybe, uh, David’s
0:33:33 going to die. My dad’s going to die. And then my mom was like, let’s just shut it down. I can’t deal
0:33:36 with it. I’m like, mom, we need the money to be able to go pay for the bill, the medical bills.
0:33:42 You know? So everyone was acting chaotic and it was like extremely difficult to manage the team and
0:33:48 try to keep people focused to do their jobs. And, uh, you know, this thing happened where, uh, one
0:33:54 evening, one of our cooks was like walking out and he had this big bag and I went over and I was like,
0:33:57 what the hell are you doing? And I realized he was stealing a bunch of steaks and like, it was just
0:34:02 steaks, but it was with a bunch of the other chefs. And I was just like, I didn’t do it for a tactical
0:34:06 reason. I just did it because I was fed up and I’m like, you’re stealing from my dying father. And I just
0:34:10 last thing I need. So I was just like, give it back. You’re fired. Go away. And they were shocked.
0:34:14 And I was like, no, no, you’re fired. You’re not allowed to come back in anymore. Um, we’ll, we’ll send you
0:34:19 your, your severance basically in two weeks, get the hell out of here. And like what, what I was
0:34:23 not anticipating is the next day, everybody showed up for work and suddenly there was actually, everyone
0:34:28 was calmer. And I think it was the transition of perception of power that they were like, they
0:34:31 want, you know, I did something harsh and yet suddenly everybody’s performance improved partially
0:34:34 because they’re like, okay, now I know we’re like the hand that feeds, but it was also like knowing that
0:34:39 there was some rules and there was a plan. And then I, I want to leave you with the thought that
0:34:44 wasn’t like my lesson was like, okay, be like the red queen all the time. That’s not
0:34:48 absolutely the way to go. That’s not leadership. But I think what I did learn is that when times
0:34:52 are difficult, people prefer to know that there’s a plan and it’s organized and there’s a solution,
0:34:57 even if it’s rules that don’t benefit them rather than having open-ended chaos. And I think that
0:35:02 was counterintuitive to me because my personality is different. I actually thrive in chaos and having
0:35:08 those sorts of complicated choices. And I, and I resent confinement, um, of any form, but,
0:35:13 but I think that that actually, for most organizations, that’s empowering and important and to articulate
0:35:17 the rules and people know that there’s a system, then people are like, I feel comfortable because
0:35:22 now I understand and it can like work in a predictable environment. And I think that part’s important.
0:35:26 So that’s something you learned running the restaurant that has helped you as a CEO. I know
0:35:31 you recently bought the restaurant. So now you’re a restaurant owner. Is there something you’ve
0:35:34 learned running a biotech company that now helps you running a restaurant?
0:35:41 Oh, so yeah. Uh, yeah. Uh, well, externalizing responsibility. So I don’t run the restaurant.
0:35:46 Uh, I bought the hotel and rest or the restaurant and some of the properties, not the full hotel. Some
0:35:52 other people bought some of the bungalows. Um, and then what I did is I basically wanted to
0:35:58 maintain the value of the property and increase it and make sure that all the people who’d, some of us
0:36:04 have worked for our family since my childhood, that their, their jobs weren’t compromised, which during
0:36:09 the pandemic where tourism was like really bad, like there was a risk of that. And so I run it essentially
0:36:13 as a, it’s a cooperative. It’s really, I’m like, I don’t extract financing from it. I’ve talked,
0:36:17 I have basically a guy that we worked with for a long time and another team member.
0:36:21 I’ve just told them like, look, my objective is for you to maintain the reputation of the place.
0:36:25 Just keep running it well and make sure. And my one requirement is I need to not think about it at
0:36:31 all. And, and, and I’m working on the universal vaccine tech. So maybe I’ll, you know, in the future,
0:36:35 I’ll want to go and fiddle around and be a restaurateur. But like right now I just needed to not think about
0:36:43 it. Um, I’ve heard you use the word hard ass a few times in other interviews. Are you a hard ass?
0:36:55 Um, I think on myself and on an expectation of detailed, I think research needs to be done in
0:36:59 a very particular process. I don’t think my team would say I’m a hard ass. I don’t, I think that,
0:37:05 um, or maybe I’ve evolved over time. I think I have exacting standards of expectation of how to get
0:37:10 things done this, but it’s not like, it’s more like me driven of anxiety than me going in and like,
0:37:15 I don’t bark at people or anything. I’m like, guys, we have to have an anxious hard ass.
0:37:20 Yeah. I have to be like, look, we have to have a set of standard, um, you know, controls. And then
0:37:23 we need to run this in a certain way and we need to have things documented. Otherwise we’re just
0:37:28 walking on quicksand and we’ll just mess up every time. So no, I don’t think I’m a hard ass. I think
0:37:32 there’s certain things where I have exacting expectations, but I also think that you have to
0:37:37 have that if you want to build a, I’ve struggled to find an example of a big company that was built
0:37:41 on technology where the CEO did not have that property. Cause I think there’s a certain
0:37:46 expectation of excellence that is required to build something great. Maybe a little bit of a hard
0:37:49 ass. A little bit of a hard ass. All right. All right. Occasional.
0:38:00 Jacob Glanville is the founder and CEO of Centivax. You can email us at problem at pushkin.fm and please
0:38:06 do email us. I read all the emails. Today’s show was produced by Gabriel Hunter Chang, edited by
0:38:12 Alexandra Gerritin and engineered by Sarah Bruguer. I’m Jacob Goldstein, and we’ll be back next week
0:38:13 with another episode of What’s Your Problem?
0:38:25 This is an iHeart Podcast.
0:00:31 you against deadly diseases. It’s a thing you get so you don’t get sick in the first place.
0:00:38 And it’s so clever and so elegant and so obviously useful. I think it is honestly fair
0:00:43 to say that vaccines are truly one of the greatest inventions of all time on the very
0:00:48 short list. They’ve saved hundreds of millions of lives. Give me all of them. Give me all
0:00:59 of the vaccines. But I got to say, the flu vaccine sucks. The flu vaccine sucks. It really
0:01:07 does. And for a somewhat simple reason. The flu virus mutates so quickly that we can’t come
0:01:13 up with vaccines fast enough to keep up with it. So every year, scientists develop a new
0:01:20 vaccine. But even in the time it takes to manufacture that vaccine, the virus keeps mutating. As
0:01:24 a result, even if you get a flu shot every year, there’s still a good chance that you’ll get
0:01:32 a bad case of the flu. Last year’s flu shot, for example, was only about 35% effective. And
0:01:38 so for decades now, scientists have asked a fairly obvious question. Is there some way to come
0:01:43 up with a flu vaccine that would work not just for the strain of flu that is circulating right
0:01:48 now, but for almost all strains of flu, including strains that haven’t even evolved yet?
0:01:58 I’m Jacob Goldstein, and this is What’s Your Problem, the show where I talk to people who
0:02:04 are trying to make technological progress. My guest today is Jacob Glanville. He’s a bioengineer
0:02:10 and an immunologist. And he’s the founder and CEO of Centivax, a company that’s trying
0:02:17 to make a universal flu vaccine, a flu vaccine that will consistently and reliably prevent people
0:02:18 from getting the flu.
0:02:23 You imagine talking to a generation that didn’t have flu anymore. They would think we were nuts.
0:02:26 They were just like, oh, yeah, every year we have a circulating pandemic. And then six months
0:02:30 later, there’s another one. And yeah, you know, 50,000 people die. But what do you do? And
0:02:34 like, that’s nuts. But we take it for granted.
0:02:40 The vaccine that Jacob’s company, Centivax, is developing for flu is likely to go into human
0:02:47 trials next year. The company is also in earlier stages of developing universal vaccines for HIV
0:02:55 and COVID, among other diseases. And wild card, they have also worked on creating a broadly effective
0:03:00 anti-venom for snake bites. We talk about snake bites later in the conversation.
0:03:06 To start, Jacob told me about the moment he first got the idea for a universal vaccine.
0:03:13 It was around 2012. He was working for the drug company Pfizer. And he wasn’t working on vaccines,
0:03:19 but he was doing something related. His job was to identify antibodies that could be used to treat
0:03:25 disease. And at this particular moment, he was studying antibodies that would bind to a particular
0:03:32 protein called PCSK9. And so I was riding back on my motorcycle one evening, and I was reflecting on
0:03:38 this problem where there’s this target called PCSK9. It kind of looks like Mickey Mouse’s head.
0:03:45 And they were really wanted antibodies against kind of where the neck is. If you get an antibody there,
0:03:50 then that can affect cholesterol and lower cholesterol. The problem is that they’re getting
0:03:54 antibodies against the ears, and they weren’t getting antibodies against the neck. And so I was
0:03:59 trying to figure out, is there an engineering way to sort of focus the immune system at arbitrary
0:04:05 sites? That would save me a bunch of time. And I started imagining, what if I were to take
0:04:13 that target, not just from humans, but from like a donkey and an alligator and a chicken and like,
0:04:18 just take a swath of different versions of that. They were different just about everywhere up in the
0:04:24 ears, but they were the same down where the neck was. And then if I mix those together and I diluted
0:04:30 each one, there wasn’t enough of any one of the species of PCSK9, then maybe only the neck would be the
0:04:34 thing which was shared across all of them and the entire immune system would focus on that.
0:04:40 So like in total, the sort of sum total of the mix, it would be like a lot of neck. The neck is
0:04:46 conserved. The neck is what is the same. And there’s only enough of that to induce the antibody
0:04:51 response. So that then if you, whatever, inject that into an animal or a person, what the person’s
0:04:53 immune system is going to see is a lot of neck.
0:04:57 Yeah. And so they finally focus on the neck instead of getting distracted by the ears.
0:05:02 That was the principle. And so I got home and then at a certain point I realized I was being an idiot.
0:05:07 And what this was, was not a way to save a few months on an antibody discovery campaign,
0:05:12 that this was a potential window opening to the, to all the Holy grail of vaccine science.
0:05:20 The Holy grail is that all of the major viruses that we’re confronted with flu influenza, HIV, Ebola,
0:05:27 these viruses mutate and change, but they always have some little spot that they cannot mutate.
0:05:31 And those spots are always super important. That’s why they can’t mutate it. Because if you
0:05:36 mutate it, the virus is no longer infectious. And normally they get away with it by having
0:05:41 distracting areas and most of the surface that can mutate. And that’s why we have to update our
0:05:42 flu shots every year.
0:05:46 Distracting meaning distracting to our immune systems, like our immune system is like,
0:05:51 oh, I like the, I like the ears. I like that shiny part on top. And that’s the part that keeps changing.
0:05:55 Yeah, yeah, yeah. Basically the conserved Achilles heel is a small site and most of the
0:06:00 surface can vary and it can’t, it gets away with not changing the critical site by varying lots of
0:06:04 stuff around it and taking advantage of the fact that the immune system doesn’t know the difference.
0:06:10 And so the ability to focus the immune system against a conserved site would be the basis of
0:06:16 a universal vaccine. Because instead of targeting one strain of flu or one strain of coronavirus or
0:06:21 one strain of HIV, you could target the shared sites that the virus is never allowed to mutate.
0:06:25 And if you do that, then you’re suddenly hitting the entire class of influenza viruses,
0:06:27 including future ones that haven’t evolved yet.
0:06:32 Right. I mean, that part of the idea is the part everybody knew already, right? Like that is the
0:06:37 relatively obvious idea. It’s like, don’t go for the part that changes. Go for the part that’s the
0:06:44 same, right? The hard thing is how do you do that? So, so had, when you describe the idea of like,
0:06:50 oh, just take a bunch of different ones, dilute them, mix them together. Nobody had thought of that
0:06:58 before? Yeah. So surprisingly not. To your point, people, since the nineties were aware of these
0:07:02 conserved sites. And so they knew where the sites were. We had crystal structures.
0:07:05 It was just, how the hell do you get the immune system to focus on those sites was the problem.
0:07:09 Yeah. And people had tried a couple of different things. They tried chopping out parts of the
0:07:14 protein, but then, then the site you’re interested in falls apart. It’s like trying to grab a snowflake.
0:07:19 It’ll melt in your hands. They tried a couple of other techniques that didn’t work out.
0:07:24 So, okay. So you have this new idea for how to make a universal vaccine that nobody’s tried before,
0:07:30 which to use flu for an example would mean you take a bunch of different strains of flu. And in
0:07:36 particular, the sort of spike protein of the, of the flu that your immune system sees, then you dilute
0:07:42 them and mix them all together in a single vaccine. So what the patient’s immune system winds up seeing the
0:07:48 most of is the part that’s the same in all those different strains, the part that doesn’t change.
0:07:55 And then ideally the patient will develop antibodies to that part, the part that doesn’t change.
0:07:59 And therefore the patient will be immune to like almost any strain of flu.
0:08:03 Yeah. And you recognize it might not work, right? You always are like, look, this is a pipe drain,
0:08:07 but like I could not go to sleep because I was like, if this works, this is such a stunning breakthrough
0:08:12 that it’s like, it’s hard to sleep when you’re thinking about that. It sort of becomes all consuming.
0:08:20 So you get this idea and you’re working for Pfizer, a company that makes vaccines, by the way.
0:08:21 What do you do?
0:08:26 Yeah. So again, I was not doing anything involving their vaccine group.
0:08:28 I was doing important for intellectual property reasons.
0:08:31 Yeah. I was not working on vaccines at Pfizer.
0:08:40 I, I, I resigned. So I did two things. I started, uh, my first company distributed bio, and I also applied
0:08:43 for the PhD program in immunology at Stanford.
0:08:46 And you do this because of your idea?
0:08:51 Yeah. Yeah. Because basically I applied to the PhD program because I was like,
0:08:56 if I’m wrong, I need to stop thinking about this. I need to surround myself with brilliant
0:09:00 immunologists who can kick holes in this. And, and I need to be able to make sure I’m not being
0:09:06 myopic. And because, and then if I’m right, I need the world to hear me. And so I need to be a card
0:09:11 carrying PhD immunologist from Stanford. So that people go, okay, this, this guy isn’t just some
0:09:11 Yahoo. Yeah.
0:09:18 Um, and then for the company side, I just saw this opportunity to be able to go test it because I,
0:09:23 originally I, I did go out and I tried to talk to some VCs and, and 2012. And I think they’re,
0:09:26 you know, predictably their answer is like, what the hell is this? And who the hell are you?
0:09:31 And you had a bachelor’s degree, right? And you’d worked at Pfizer for a couple of years,
0:09:35 like a million other people. So, so not, you know, you can’t blame them. I was like,
0:09:40 I guess I’m nobody right now. Let me go fix that. Yeah. And, uh, and so I, I decided that
0:09:45 I was going to go found a company because there was some, there was some work I was doing at Pfizer
0:09:49 that I’d published, created some publications on using the deep genomic sequencers to look at the
0:09:53 immune system and then building better antibody libraries with what we learned about that.
0:09:57 And I realized there was a business that could be built on that. And my intention was to build
0:10:02 that business and use it to subsidize some of the early proof, uh, de-risking experiments on this
0:10:07 universal vaccine concept. And, and so that’s what I did. So I just did both for five years and didn’t
0:10:12 sleep that much. And until the PhD graduated from that. And then later I sold the first company
0:10:16 distributed bio. So the company you start, you’re selling your, your clients are drug companies,
0:10:21 essentially. Right. But you’re doing that. That’s sort of your side hustle. That’s sort of funding
0:10:30 your, your vaccine dream. Right. And while you’re doing that, you start doing this research on your
0:10:37 vaccine in pigs in Guatemala. Right. Yep. Tell me about that. Um, the background is I grew up in
0:10:43 Guatemala. My parents are Americans, but they met in Guatemala in the seventies and they built this hotel
0:10:49 restaurant with my grandmother. Hippie dream. Yeah. The hippie dream. That’s exactly what it is.
0:10:53 There’s, there’s small hippie enclaves down there. And then there’s most of the village is
0:10:57 Zutawil Mayan. And then there’s Cachiquels and some other Mayan communities. And it’s, it’s very
0:11:02 beautiful lake. So it makes sense that the hippies would go there. Yeah. Uh, the civil war largely drove
0:11:07 them away, but my family, when I was a little boy, they went down there to try to fix up and sell the
0:11:12 property. And then one thing led to another and we ended up becoming innkeepers. And so I grew up in,
0:11:18 in the village. Um, I think it probably had an effect on my interest in immunology in the first
0:11:22 place. Uh, and, and I had this connection to Guatemala and I ended up maintaining a connection
0:11:29 to USAC, which is the university of San Carlos, the national university. And so fast forward in my
0:11:35 career too, when I was thinking about universal vaccines, like one of my, I say one of my deep
0:11:40 impressions left from some work at Pfizer was this, I was very impressed with a group that was
0:11:45 doing animal health work because I felt like instead of using mice, they would often ask what’s the most
0:11:51 relevant and similar animal model to humans for this indication. Mouse is not a person like no animal
0:11:56 is a person, but you can find something that’s a closer fit and, and waste less time on failed
0:12:00 translation. Yeah. And so I liked, I had this technology. I was trying to figure out where to
0:12:06 apply it. I actually called one of the guys and I was like, what’s the veterinary market that has
0:12:12 rapidly mutating pathogen. That’s also found in humans. And he said, it’s definitely flu and pigs.
0:12:17 They get the flu. In fact, they transmit it to humans. And so things are definitely not as convenient
0:12:21 as mice, but I felt that the data would be much more meaningful because they actually get the flu.
0:12:29 So I ended up doing it back in Guatemala with Erwin Calgua, my collaborator at the University of San
0:12:34 Carlos, and some property that my father had. So I ended up making some calls. I found out we could
0:12:40 get the pigs. There was a vet who was involved in the H1N1 2009 pandemic shift monitoring.
0:12:44 You’re doing it in Guatemala because it’s cheaper, basically? You’re offshoring your research?
0:12:49 Yeah. It’s way cheaper. Yeah. Radically cheaper and faster. I think the cycle time is astonishingly
0:12:54 slow to do animal studies and ask for grants. You’re lucky to get a study done once every two and a half
0:13:00 years, according to the US model. Whereas in Guatemala, the costs were radically cheaper. I could
0:13:06 build a facility to spec. And I’m an engineer, so I need to be able to do cycles. And so this enabled me.
0:13:10 I think we ran five studies there over a couple of year period. We were able to go pretty quickly,
0:13:16 go in and rapidly de-risk this universal vaccine technology in a way that was economically feasible,
0:13:21 given the growing profits, but still finite profits that I had from the antibody discovery
0:13:22 and software side of the business.
0:13:28 So when you’re doing those pig studies, I mean, just to return to your initial idea of
0:13:34 using essentially different strains, let’s say, you got to figure out what’s the right concentration.
0:13:40 Because if you do too little, you don’t get any meaningful immune response. And if you do too much,
0:13:44 then you’re getting immune response to the parts that are not conserved, to the parts that you don’t
0:13:45 want immune response to.
0:13:49 Exactly. I was also just proving the concept, right? Because I think there’s definitely people
0:13:54 who are like, this isn’t going to work. There’s no way. And look, if I’m wrong, then it doesn’t
0:13:58 matter if I put 15 things in. If each one’s below the dose and they’re not interacting like I was
0:14:03 hypothesizing, then you should see no immune response, right? So I could have just been wrong.
0:14:06 That’s the other thing. I was testing to see, does the principle hold? And the answer was
0:14:07 definitively yes.
0:14:13 So, okay. So you have this idea that it works. Somewhere around here, you sell, I don’t know
0:14:17 which one is the side hustle and which one is the main hustle. I guess vaccinating pigs in
0:14:21 Guatemala sounds like a side hustle, even though it’s the thing you really care about, right?
0:14:32 You sell distributed bio and you spin out, sent to VAX, the vaccine company, right? And then what?
0:14:33 Then where are you?
0:14:42 Yeah. So it was a good time. So we got, the Gates Foundation had awarded us this, in the pandemic
0:14:47 threat grand challenge award to test the vaccine, no longer in Guatemala, but up in American facilities
0:14:52 that had biosafety containment so that we could challenge the animals who’d been vaccinated
0:14:58 with these strains that had evolved after the mixture. So we deliberately pretended it was 2007
0:15:04 and only included strains up to 2007. Then we challenged the animals with the 2009 pandemic
0:15:07 shift virus, a 2012, a 2017 virus.
0:15:11 That’s a big question, right? It’s like testing something that’s out of the model, right?
0:15:17 Like it’s saying, okay, we give somebody this vaccine and then there’s a new kind of flu.
0:15:18 Does it work?
0:15:19 Yeah.
0:15:19 Yeah.
0:15:23 And it felt that that was essential, which by the way, those same pigs, we pulled their serum
0:15:27 out of the freezer over the last couple of months and they neutralized the H5N1 that’s currently
0:15:30 outbreaking in cows and chickens and some people.
0:15:30 Uh-huh.
0:15:31 The bird flu.
0:15:32 The bird flu everybody’s scared of.
0:15:33 Yeah, it creates super broad immune response.
0:15:34 Yeah.
0:15:42 So the timing was good. CRL wanted to buy. I was happy to do it. And, uh, my condition
0:15:46 was, I’m like, look, I want to take this universal vaccine technology, uh, with me to a new company.
0:15:53 And they agreed to that. That was December 31st, 2020 is when the, when the sale completed.
0:15:54 And so basically January 1st.
0:16:00 That is a remarkable time to go all in on a universal vaccine, December 31st, 2020.
0:16:07 So we transitioned over January 1st, 2021. Uh, I am now the CEO and founder of Cinevacs. And I,
0:16:11 I started calling an army of geniuses of the best people that I’ve worked with to gather together.
0:16:13 And I was like, look, this is going to be the big one where.
0:16:17 It’s like a, like a heist movie, like Ocean’s 11 or something.
0:16:21 Yeah. It was like the best people of my entire career I worked with. You don’t need a lot. You
0:16:25 just need every person to be exceptional. And like, if we do our jobs, right, we touched the long
0:16:25 arc of history.
0:16:30 Yeah. So, so what have you figured out? Like what have been the
0:16:33 key things you’ve figured out since then?
0:16:39 We identified, uh, a couple extra people we brought in, including Jerry Sadoff. He’s this
0:16:47 guy who’s has more vaccines approved than anyone alive. So things like Gardasil, MMRV that all
0:16:52 children take, you have the coronavirus vaccine from, from J and J the one shot. And, you know,
0:16:56 I think 14 vaccines have been approved under his watch. It wasn’t just that he had done a huge
0:17:01 amount of like the modern vaccines that define the modern health era. It’s that his hit rate
0:17:06 was unusually high. Like it wasn’t like he worked on a hundred to get to those 14. He had like his
0:17:11 rate ratio of success was unusually high. And that told me I wanted to work with them. And so I
0:17:15 called him up and went out to have dinner with them. And I was like, Jerry, you told me this
0:17:19 universal vaccine technology is the only thing you thought was worth a damn. Like, come, come join me
0:17:23 and like, let’s kick a hole in the universe. And so he came. And the reason I’m telling you this is
0:17:28 that he, he didn’t just come in with phenomenal clinical plans, which he did. Uh, he also came
0:17:31 in with some strategies where he’s like, one of the things I’ve noticed for both the coronavirus
0:17:37 vaccines and the RSV vaccines was that the folks who added in little mutations to keep those spikes
0:17:42 stable, those vaccines were successful. And the folks who didn’t add in good stabilizing mutations,
0:17:47 their vaccines were unsuccessful. Huh? And he said, I think that that’s just a critical thing.
0:17:52 You want to trap these spikes in their stable form so the immune system can target what the
0:17:56 spike looks like before it attacks a cell or before it falls apart to confuse the immune system.
0:18:01 So just to be clear, like the, the spike proteins, it’s the, the hemagglutinins that,
0:18:07 that are in nature on the outside of the, of the, of the flu virus, they have a three-dimensional
0:18:12 shape, right? Yeah. They can change three-dimensional shape. And that actually turns out to be important
0:18:16 for sort of simple mechanical, like a key fitting into a lock reason.
0:18:22 Right. And it’s, and they don’t, if you rip them off the virus as you are, when you’re presenting
0:18:25 them in this vaccine, necessarily stay in the shape you want them to stay in. That’s a problem.
0:18:30 Yeah. They’re kind of like a little three-pronged grappling hook and they change shape in order
0:18:34 to like hook into the cell membrane and then tear it open. And they’re designed kind of like with
0:18:38 hinges because they need to be able to be mobile and make changes. And so this protein is not inherently
0:18:43 stable, but what you want is you want the thing very stable because you want the immune system to train
0:18:49 on defeating the trimer when it’s in, it’s sort of cocked, cocked and loaded, but prior to shoot
0:18:54 position. Yeah. And, and we’ve seen with RSV and coronavirus that that was absolutely essential
0:18:58 for the successful vaccines. Right. And so anyway, Jerry came in and was like, we should do this with
0:19:03 flu. I had a bunch of experience stabilizing proteins from work. We did stabilizing antibodies
0:19:10 at Pfizer and then also at my company, my distributed bio. And so we ran a quick campaign and we identified
0:19:15 these great stabilizing mutations and they had like a pretty stunning effect on the quality of the
0:19:21 immune response. So you’re doing this basically atomic level engineering of the proteins, right?
0:19:22 Yep. That’s a thing. Go on. What else?
0:19:27 And then the other thing, the major thing we’ve done is we started the manufacturing. We advanced the
0:19:32 program, not just for flu, but we’re also, we have data validating the universal coronavirus
0:19:40 vaccine. We’re testing on HIV. We’re testing on malaria and a number of other pathogens right now
0:19:44 to be able to create a portfolio. So those have been some of the major activities in the last couple of
0:19:50 years. When are you doing human clinical trials? Yeah. So we’ve got about nine months left of
0:19:55 manufacturing or eight months of manufacturing. And then you, you spend a month getting permission
0:20:01 from the FDA to start your, your study. And then we’d start human trials. So, okay. So next year
0:20:05 you’re starting human trials next year. So, so when you think about the future, the future of the company
0:20:08 of your work, like what, what are you worried about?
0:20:14 So I worry about less and less things. And then the things I worry about evolve. So in terms of,
0:20:21 is it going to be safe? I worry about that extremely little. Um, we have been vaccinated with
0:20:28 influenza, HA protein since the 1940s. It’s actually the best validated diverse class of versions of HA
0:20:32 compared to any other vaccine that’s been tested. And it’s the tolerance, the history of safety has been
0:20:39 extremely good. We’re using the, um, Pfizer biointech MRNA chemistry. So you can get a
0:20:44 non-exclusive license to it. That’s the same one they used for the COVID vaccine. Yeah. So it’s been
0:20:49 in billions of people. So we know what the safety profile is. So safety, I’m not concerned about in
0:20:54 terms of efficacy, like how well it works. Uh, I basically don’t believe in any one animal’s immune
0:20:59 system because you could always overfit. The immune system could overfit in a certain bizarre and
0:21:07 unpredictable way. And so we’ve tested this in pigs, but also ferrets, also rats, also mice, also cows,
0:21:13 and also human immune organoids, which is organ donors offer their lymph nodes. They’re smushed up and
0:21:16 you basically create a bunch of little mini lymph nodes from a donor and you can vaccinate them under
0:21:22 different conditions to see how someone with a lifetime of immune memory, including to flu and vaccines
0:21:28 would respond to our vaccine or a control vaccine. And when we did that, as well as all the other
0:21:34 animals, we consistently saw this universality effect. And so going into the human trials,
0:21:40 I think we’re pretty bullish that the effect is going to be dramatically better than, uh, the
0:21:45 current vaccine. So I think we’re going in assuming that the human trials probably will perform well,
0:21:49 but I want to say I won’t sleep well at night until I get that data. And I’m like, okay, yeah,
0:21:54 we’re, we’re, we’re on solid footing. I, I, we’ve done everything I can to de-risk it with these
0:21:58 other organisms and, and even human immune organoids. And now it’s time to run it in humans.
0:22:04 Um, fundraising is always a headache where we’ve got now at least multiple groups gathering around
0:22:08 with term sheet options and we’re looking at them, but it’s, uh, it’s been, I would just to put it
0:22:12 lightly, a difficult period for biotech fundraising that we’ve managed to survive where a number of
0:22:17 other companies have not. But, uh, you know, I’m, I’m probably gained some gray hair and probably,
0:22:20 uh, you know, took away some of my health span as a consequence of surviving this period.
0:22:25 Uh, I mean, does that last thing mean you’re afraid of running out of money?
0:22:30 That’s what, I mean, every company worries about that. That’s the nature of venture. We’ve managed
0:22:35 to pull it together and we just got this grant, which covers us. But the, the, the fear is that
0:22:39 we’re stuck, that we, we need to go continue raising money so that we can go pay for the rest of
0:22:45 manufacturing and pay for clinical and, and, and arm for the next parts. And, and to be blunt,
0:22:50 this has been an absolutely terrible period in biotech. So we got 75% off on all of our equipment
0:22:54 for my entire laboratory. Cause we got it from auctions. A lot of the stuff was in like new stuff
0:23:00 in boxes where a company just ran out of money and they’re stuck. And I benefited from it. I’ve
0:23:05 benefited from being able to hire remarkable people that otherwise were struggling to find an opportunity
0:23:10 because of it’s, we’ve basically lived in this, like a little bit of a biotech hangover after I think
0:23:15 there was too much investment and sometimes it’s some pretty goofy stuff during the pandemic for biotech.
0:23:19 And I think we’re in this like a little bit of a headache, a little bit of a macro economic global
0:23:23 uncertainty area. And those things have both slammed up against biotech in an unproductive way.
0:23:30 Yeah. Um, so, okay. What’s the happy version of the story?
0:23:37 The happy version is that our vaccine works the same as it has in all those animals and organoids
0:23:43 that we’ve seen. We bring it forward. Universal vaccine just becomes the vaccine because that’s
0:23:48 suddenly a vaccine that you take and you don’t get sick. The first thing it does is it creates
0:23:54 a massive improvement in global health. And then the major impact of, you know, flu kills people,
0:23:59 right? It gets a lot of people sick. People lose a lot of time from school, pregnant women in their
0:24:04 second trimester to get flu or seven times more likely to have a child with, with schizophrenia and
0:24:10 their adult, like it has, there’s a bunch of like squali and consequences. But the biggest effect is that
0:24:13 when this gets out there, the pandemic era is over.
0:24:18 Uh-huh. And when you say pandemic, you mean flu pandemic, but yeah, the flu pandemics are over.
0:24:23 Yeah. Which is our most common source of pandemics. We had five in the last hundred years. We had,
0:24:28 you know, two or three per century before then. So they got faster. Yeah. We have a lot more people.
0:24:34 We have these pig mega farms. Like we need to fix this. And with this vaccine, you no longer have a
0:24:39 pandemic era because you have a decent proportion of the population that’s already immune to the new
0:24:44 virus strains before they hit. And that’s what the new world looks like. And so that’s the happy version
0:24:50 for flu. But our intention is to do that for every pandemic pathogen, to just one by one go and end the
0:24:55 pandemic era, to come up with countermeasures that first protect the world from pandemics, the medical,
0:25:01 personal and economic costs. Second, protect the world from just major outbreaks. And then ultimately,
0:25:06 I want to have these same tools can arm future decades to attempt eradication campaigns that
0:25:14 previously were not possible. And that’s the future we want to go. We’ll be back in just a minute.
0:25:31 Um, let’s talk about snake bites. All right, let’s do it. Um, how’d you get into the snake bite
0:25:41 business? Yeah. So it was 2017. And I think it was because the world health organization was
0:25:48 announcing, you know, the neglected tropical disease nature of snake bite, kind of declaring it a
0:25:53 neglected tropical disease. Basically saying hundreds of thousands of people are killed or
0:25:58 very badly wounded every year by snake bites. It’s not just some weird thing.
0:26:03 And not enough people are trying to develop countermeasures. And I think what had happened…
0:26:07 Because most of the people who are, who die or are severely injured are super poor.
0:26:15 Yeah. Yeah. That’s, uh, it reminds me of, uh, Monty Python, where they have the Roman Senate and
0:26:19 someone goes, what do we do about the poor? And then all in unison, they put up their hands and
0:26:20 they’re like, fuck the poor. All right, next.
0:26:24 That’s the neglected tropical disease story.
0:26:31 The fundamental problem. Yeah. I think also that, I mean, like, to be fair, I don’t want to be fair,
0:26:36 but like the companies that make anti-venom, most of them are kind of doing it as a public service as
0:26:40 a loss because most of the people who need anti-venom of the millions of bites per year,
0:26:44 they’re, they’re poor. They’re subsistence agriculturalists and their children and people
0:26:50 who live in rural environments. Um, and if you take that market, which is probably like five to
0:26:55 600 million total per year, but it’s fractured across 30 to 40 products. Each of those things
0:27:00 is pretty unattractive. Just to be clear, because you need different anti-venom for different snakes
0:27:04 for different kinds of things. Yeah. There currently is no universal anti-venom on the market. And so
0:27:08 people had started ending programs to make certain types of anti-venoms. And I think that was happening
0:27:14 in 2016. So then in 2017, the World Health Organization brings some attention to this. And then I, you know,
0:27:19 I started thinking about it. I, you know, in my village, we had snake bites sometimes and I just
0:27:23 like, I like topical diseases, particularly if they interface with cool bioengineering
0:27:29 and I’d been working on the universal vaccine work. And so I started wondering, I’m like, you know what?
0:27:34 I wonder if that same idea of their conserved Achilles heel that’s found across all flu
0:27:41 or all HIV. I wonder if snake venom toxins have that, because if that’s true, maybe you don’t need
0:27:48 to make 650 different anti-venoms. Maybe it’s actually that you only make one cocktail of broadly
0:27:51 neutralizing antibodies and it could work against all snakes, a universal anti-venom.
0:27:58 And so I did a little, you know, playing around on my computer. And sure enough, there’s basically
0:28:04 like 10 major toxins that all snakes use. Nature’s lazy. And then when I pulled up a bunch of sequences
0:28:09 from a bunch of different snakes and I compared where they varied, where they mutated relative to
0:28:14 each other versus not, again, I found a little conserved spot and it’s the, it’s the business end,
0:28:18 right? Cause these toxins can mutate except they can’t mutate right where they need to go bind your,
0:28:23 your neurons, your nicotinic acetylcholine receptor to paralyze you and so forth.
0:28:27 And so at that point I got pretty stoked where I was like, I’m pretty sure this is, and like at the
0:28:31 time no one had been talking about broadly neutralizing antibodies outside of viruses.
0:28:35 And I was like, this is so cool. And so then I was like, all right, where do I find a person
0:28:40 who, uh, has been bent a couple of times? Right. And I was like looking for a clumsy snake researcher.
0:28:46 Like there’s like a site in, uh, Costa Rica. There’s a place in Arizona. There’s some places
0:28:51 in India where I was reaching out and like, I was kind of coming up empty. And then I don’t know
0:28:56 how, somehow like I desperately just started like Google searching. And, uh, and I found these insane
0:29:03 articles about this guy named Tim Freedy who had spent like at the time over 17 years, self immunizing
0:29:10 hundreds of times with 16 different species of snake. What he did is he milked the snakes. He weighed
0:29:15 out microgram initial doses and administered it. And then he dose escalated over a period of months up
0:29:19 until the point that he took milligrams. And it was only after he built up that immunity, then he would
0:29:25 then have the animal, the animals challenge him. Cause like no one lives people, you can’t live from a
0:29:29 mamba bite and he’ll kill you. And yet he is able to take it. You see that video. What you don’t see
0:29:33 is he spent about nine months building up immunity against it by starting with microgram trace doses.
0:29:39 That’s crazy. So you’re like, that guy is, is the walking universal antivenom.
0:29:44 Yeah. If anybody has the secrets of universal antivenom, it’s pumping through this guy’s veins
0:29:49 right now. And so I was like, I have to meet him. I couldn’t find his contact information anywhere
0:29:53 online. And so I contacted the reporters and one of them put me in touch with them and had his number.
0:29:57 And so I had this call and I told, I remember it super clearly. And where I was just like, look,
0:30:02 I know this may be awkward, but I would love to get my hands on some of your blood.
0:30:06 And his response was, uh, I’ve been waiting for this call for a long time.
0:30:10 And, and so what happened?
0:30:16 And then what I do is we just scheduled a 28 days apart, two blood draws and each one was for 20
0:30:20 milliliters. So there was no risk as to the, the blood draw amount. This is like a couple tubes.
0:30:28 Um, and so then that, that got sent over to my lab. I then processed it in my, and I separated out the
0:30:32 serum and the cells and from the serum, I wanted to check his work. I think, you know, a story,
0:30:36 you know, seemed credible and stuff, but I wanted to confirm. And so I’d ordered a series of snake
0:30:41 venoms, which by the way, it is suspiciously easy to order the venom of venomous snakes.
0:30:47 I have learned during this project. Um, I was like, this should not be this easy anyway. So I,
0:30:51 I had a bunch of panel of snakes, some that he said he had immunized against. And I also picked ones that
0:30:52 he never had.
0:30:55 Oh, interesting. This is testing the universality.
0:30:59 Yeah. Yeah. And so I tested his sera and I also tested mine and a couple other control sera on this,
0:31:05 on the, the venoms. Now the control people like me who’ve have never been bit, we had no response
0:31:10 to the serum. He had blazingly high responses to all the venoms, including the ones he had never been
0:31:12 exposed to, including new genera, like very different snakes.
0:31:19 So based on this, right, you come up with this anti-venom cocktail that, uh, that seems like
0:31:25 it could work against not all venomous snakes, but a lot, a lot of different kinds of venomous snakes.
0:31:30 Um, you publish a paper about this in the journal sell. Where does it go from here? What happens next?
0:31:35 Um, we’ve reached out to the welcome trust and to some other groups that might be interested in this.
0:31:39 We’ve also reached out to, I guess I won’t say their names, but there’s some pharmaceutical
0:31:44 companies that develop anti-venom to try to see if this is something they’d be interested in doing a
0:31:49 partnership on to pick up. I think my feeling is that I would ideally like to have a pharmaceutical
0:31:55 partner to go develop this with, um, or a massive support from some foundation because otherwise it’s,
0:32:01 you can make it profitable. You can unfracture that market and you could be manufacturing this and serve
0:32:09 maybe a $500 million per year market. But to get there, you have to go spend at least 10 and probably
0:32:14 more like $20 million on GMP and some other early activities and then 25 million for clinical.
0:32:19 And I think it’s hard to imagine who’s going to put that money up front for what is a relatively small
0:32:23 profit, which is the whole frustrating aspect of neglected tropical diseases.
0:32:25 That’s why they’re neglected. Yeah.
0:32:30 We’ll be back in a minute with the lightning round.
0:32:50 Okay. Last thing is a lightning round. Um, so as I understand that you dropped out of school to run
0:32:56 your family in hotel restaurant when you were in high school or you took a year off high school,
0:32:59 what’s one thing you learned from that?
0:33:03 Yeah. I think one thing I learned is that people on teams don’t,
0:33:10 that people do not crave chaos. I think people want to know what the people are calmed down by
0:33:15 knowing that their rules, even if the rules don’t benefit them. And I dropped out to go run the
0:33:19 restaurant and I was like 15 year old kid. Uh, and you know, initially people didn’t really listen
0:33:24 to me, you know, it was just like a crazy time. And that was crazy for the employees. Cause the
0:33:29 employees are like, I don’t know, like your son’s here, but maybe, uh, you know, maybe, uh, David’s
0:33:33 going to die. My dad’s going to die. And then my mom was like, let’s just shut it down. I can’t deal
0:33:36 with it. I’m like, mom, we need the money to be able to go pay for the bill, the medical bills.
0:33:42 You know? So everyone was acting chaotic and it was like extremely difficult to manage the team and
0:33:48 try to keep people focused to do their jobs. And, uh, you know, this thing happened where, uh, one
0:33:54 evening, one of our cooks was like walking out and he had this big bag and I went over and I was like,
0:33:57 what the hell are you doing? And I realized he was stealing a bunch of steaks and like, it was just
0:34:02 steaks, but it was with a bunch of the other chefs. And I was just like, I didn’t do it for a tactical
0:34:06 reason. I just did it because I was fed up and I’m like, you’re stealing from my dying father. And I just
0:34:10 last thing I need. So I was just like, give it back. You’re fired. Go away. And they were shocked.
0:34:14 And I was like, no, no, you’re fired. You’re not allowed to come back in anymore. Um, we’ll, we’ll send you
0:34:19 your, your severance basically in two weeks, get the hell out of here. And like what, what I was
0:34:23 not anticipating is the next day, everybody showed up for work and suddenly there was actually, everyone
0:34:28 was calmer. And I think it was the transition of perception of power that they were like, they
0:34:31 want, you know, I did something harsh and yet suddenly everybody’s performance improved partially
0:34:34 because they’re like, okay, now I know we’re like the hand that feeds, but it was also like knowing that
0:34:39 there was some rules and there was a plan. And then I, I want to leave you with the thought that
0:34:44 wasn’t like my lesson was like, okay, be like the red queen all the time. That’s not
0:34:48 absolutely the way to go. That’s not leadership. But I think what I did learn is that when times
0:34:52 are difficult, people prefer to know that there’s a plan and it’s organized and there’s a solution,
0:34:57 even if it’s rules that don’t benefit them rather than having open-ended chaos. And I think that
0:35:02 was counterintuitive to me because my personality is different. I actually thrive in chaos and having
0:35:08 those sorts of complicated choices. And I, and I resent confinement, um, of any form, but,
0:35:13 but I think that that actually, for most organizations, that’s empowering and important and to articulate
0:35:17 the rules and people know that there’s a system, then people are like, I feel comfortable because
0:35:22 now I understand and it can like work in a predictable environment. And I think that part’s important.
0:35:26 So that’s something you learned running the restaurant that has helped you as a CEO. I know
0:35:31 you recently bought the restaurant. So now you’re a restaurant owner. Is there something you’ve
0:35:34 learned running a biotech company that now helps you running a restaurant?
0:35:41 Oh, so yeah. Uh, yeah. Uh, well, externalizing responsibility. So I don’t run the restaurant.
0:35:46 Uh, I bought the hotel and rest or the restaurant and some of the properties, not the full hotel. Some
0:35:52 other people bought some of the bungalows. Um, and then what I did is I basically wanted to
0:35:58 maintain the value of the property and increase it and make sure that all the people who’d, some of us
0:36:04 have worked for our family since my childhood, that their, their jobs weren’t compromised, which during
0:36:09 the pandemic where tourism was like really bad, like there was a risk of that. And so I run it essentially
0:36:13 as a, it’s a cooperative. It’s really, I’m like, I don’t extract financing from it. I’ve talked,
0:36:17 I have basically a guy that we worked with for a long time and another team member.
0:36:21 I’ve just told them like, look, my objective is for you to maintain the reputation of the place.
0:36:25 Just keep running it well and make sure. And my one requirement is I need to not think about it at
0:36:31 all. And, and, and I’m working on the universal vaccine tech. So maybe I’ll, you know, in the future,
0:36:35 I’ll want to go and fiddle around and be a restaurateur. But like right now I just needed to not think about
0:36:43 it. Um, I’ve heard you use the word hard ass a few times in other interviews. Are you a hard ass?
0:36:55 Um, I think on myself and on an expectation of detailed, I think research needs to be done in
0:36:59 a very particular process. I don’t think my team would say I’m a hard ass. I don’t, I think that,
0:37:05 um, or maybe I’ve evolved over time. I think I have exacting standards of expectation of how to get
0:37:10 things done this, but it’s not like, it’s more like me driven of anxiety than me going in and like,
0:37:15 I don’t bark at people or anything. I’m like, guys, we have to have an anxious hard ass.
0:37:20 Yeah. I have to be like, look, we have to have a set of standard, um, you know, controls. And then
0:37:23 we need to run this in a certain way and we need to have things documented. Otherwise we’re just
0:37:28 walking on quicksand and we’ll just mess up every time. So no, I don’t think I’m a hard ass. I think
0:37:32 there’s certain things where I have exacting expectations, but I also think that you have to
0:37:37 have that if you want to build a, I’ve struggled to find an example of a big company that was built
0:37:41 on technology where the CEO did not have that property. Cause I think there’s a certain
0:37:46 expectation of excellence that is required to build something great. Maybe a little bit of a hard
0:37:49 ass. A little bit of a hard ass. All right. All right. Occasional.
0:38:00 Jacob Glanville is the founder and CEO of Centivax. You can email us at problem at pushkin.fm and please
0:38:06 do email us. I read all the emails. Today’s show was produced by Gabriel Hunter Chang, edited by
0:38:12 Alexandra Gerritin and engineered by Sarah Bruguer. I’m Jacob Goldstein, and we’ll be back next week
0:38:13 with another episode of What’s Your Problem?
0:38:25 This is an iHeart Podcast.
Jacob Glanville is the founder and CEO of Centivax. Jacob’s problem is this: Can you create a vaccine that protects people against almost all strains of flu – even strains that haven’t evolved yet?
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