Netflix Docu-series Star Jacob Glanville Returns To Talk About How The Pandemic Ends—and His New Company

In March of 2020, as SARS-CoV-2 was first sweeping the globe, Jacob Glanville joined Harry on the podcast to talk about the pandemic and how the kinds of antibody therapies being studied by his company Distributed Bio might help.  At the end of 2020, Charles River Laboratories bought Distributed Bio on the strength of its computational immunology platform—which automates the discovery of antibody therapeutics. But Charles River let Glanville spin off the research programs he’d been pursuing, which included neutralizing antibodies to treat influenza and coronaviruses. And now those programs have been rolled up into Centivax, a South San Francisco-based biotech startup where Glanville is once again CEO.  Glanville returns to the show this week to talk about what’s gone right—and wrong—in the biopharma business during the coronavirus crisis, how the pandemic’s end might play out, and why he sees such promise for antibody therapies against coronaviruses, drug-resistant bacteria, and even snake bites.

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Transcript

Harry Glorikian: Hello. I’m Harry Glorikian, and this is The Harry Glorikian Show, where we explore how technology is changing everything we know about healthcare and life sciences.

Almost two years ago, in the very first weeks of the coronavirus pandemic, we had a guest on the show named Jacob Glanville.

He had built a company called Distributed Bio around a new computational immunology platform that was designed search for new antibody therapies against a range of infectious diseases, potentially including coronaviruses.

We had a frank discussion about how quickly the biotech and pharma industries would be able to move to help stop the pandemic, and how antibody therapies might fit in.

And that conversation went on to become one of our most-listened-to episodes ever.

I wanted to have Jake back on the show, for a couple of reasons.

Obviously, we’ve been through a lot over the last two years, and I wanted to hear where Jake’s head is at today about whether and when we’ll get to the point where COVID-19 is under control and we can settle into some kind of new normal.

But in the meantime, there were some big changes in Jake’s world.

He sold Distributed Bio to a giant biopharma services company called Charles River Laboratories.

As you’ll hear in our conversation, Charles River was mainly interested in the computational immunology platform, and they were happy to let Jake hold on to the therapeutics programs he was pursuing.

Those included a potential universal vaccine against influenza, or the flu, and coronavirus, as well as a vaccine for HIV. They’re even doing some fascinating work on antivenoms to treat snake bites.

All that science got repackaged into a biotech startup in South San Francisco called Centivax where Jake is once again the CEO.

A couple of his former Distributed Bio colleagues came along as chief science officer and chief operating officer.

So I invited him back to hear about progress at Centivax, and also get his thoughts about where the pandemic is headed.

So here’s my full conversation with Jake Glanville.

Harry Glorikian: Hey, Jake, welcome back to the show, it’s great to have you again. It’s only been two years in the world has completely changed from what it was two years ago. Good to have you back.

Jacob Glanville: Hey, thanks for having me on again. It’s great to see you.

Harry Glorikian: So. Before we talk about your companies, your research, you know, I think people would love to hear your high level thoughts of where we are now in this coronavirus pandemic. I think the last time we had you on the show was March of 2020. It was literally just the first wave was hitting. Now it’s almost two years later. What has gone better than you expected in the science and political and public health? And what do you think is gone worse?

Jacob Glanville: Sure. Yeah. So, yeah, wow. What a wild ride the last two years have been. So there’s some things that have gone definitely better than I expected. There’s definitely been some things that have gone worse and. We’re we’re much better off than we were two years ago, but I think also it’s important not to get unrealistic and thinking this is just going to go away. So the the areas where if I look back that we did really well, we got a bit lucky that these new vaccine technologies were very effective. That wasn’t necessarily the case. There are some viruses and other pathogens that vaccines just don’t work that well for. And it turns out they work pretty well for the coronavirus and that’s helped. And they they developed them in record time and produced a lot. And that has reduced the number of deaths and significant illnesses and protects from long COVID. We’re starting to see as well, and that’s really good news. I think that’s been impressive.

Jacob Glanville: The areas where I’ve been underwhelmed, I think there wasn’t enough attention paid to to therapies and treatments. We are fortunate now that there’s this very nice looking, there’s some good antibodies that came out. Most of them got washed away by the Omicron variant. The Vir antibody still looks pretty effective so far, but larger than that, the Pfizer Paxlovid therapy. This is a pill that doesn’t require binding to the outside of the virus mutates a lot. It interferes with the virus’s ability to chop up and make copies of itself inside of a cell. And that’s that’s going to be a game changer. I think people aren’t fully realizing how much of a game changer that is, and that’s good. But I think we could have had more of these kinds of treatments if there was attention on the reality that we’re going to need treatments and not just vaccines. The other areas where I wish there had been more effort done and we still need more effort are in the manufacture of enough vaccines. So right now, we don’t have the ability as global ability to make enough vaccine before the virus changes a lot. Right now, the current vaccines are giving you, they’re the original virus. This thing’s already gone through multiple generations of new alpha, beta, gamma, delta, epsilon variants of concern. And so we’re kind of living in that flu-like world of the vaccine, always being pretty outdated to the circulating variant.

Jacob Glanville: And like right now, there actually is no way to produce enough vaccine in time to vaccinate the world before the thing changes. So we’re never going to have enough. The Third World had to wait in line and not get as enough vaccine. So Guatemala, where I grew up, they have only really 30 percent of the population have been vaccinated so far. Another 10 percent has had one shot. So they’re not even going to have a reasonable vaccination level of like the vaccine, the virus from two years ago before new generations of vaccine come out. And those are going to go to the First World first again. So right, that’s something that needs to get solved. I think there’s also just in general, I was underwhelmed by how the world cooperated to address this, and I think this speaks to the need of a pandemic treaty.

Jacob Glanville: I think and I’m glad to hear that there’s a discussions around this, but really, realistically, it’s a major global collective goods problem. This is a virus which is not going to go away. It’s going to get more manageable and there’s going to be new pandemics coming in the future. We need a global pandemic treaty to make it so that we can better coordinate responses, surveillance and just a global reaction in a coordinated fashion. Part of the problem with this is that every country had different policies and the sort of like “deal with it your own way” policies caused a lot of problems with the realistic need that if you want to stop a big virus like this, you need every nation to act like well-marshalled troops to coordinate their response efforts. And that hasn’t been fixed. And it really it should be fixed because that won’t just help us with this virus and help us with all the other pathogens we’re currently dealing with and the new ones that are going to be coming out of the woods as we march into the future.

Jacob Glanville: Part of that would also be like with Omicron. It came out of South Africa, or they detected it first. It could have come from a nation that wasn’t doing surveillance, and then South Africa was like, “Hey, what’s up, guys? Like, we are the ones who actually warned everyone about this, and then you guys just blocked all of our travel and isolated us.” Like, that’s going to actually encourage nations, I could imagine many nations being, like, “You know what, let’s not test because we can’t afford to have people block us.” That’s crazy. And that’s esily addressed with, like, you know, in the U.S., we have a shared fund of federal funds to be able to enable disaster relief. So if any state gets particularly hit, the other forty eight lift them up and a similar system should be in place to provide disaster relief funds because a site which is heavily impacted, to get relief funds to say, “Look, we’re going to quarantine you guys, you guys need to do all this extra stuff, but here’s a bunch of money to do it because you’re protecting all of us, so the problem doesn’t reach us. So, handle it well and don’t be afraid to report.”

Jacob Glanville: And so those are areas where I’m not so impressed, I guess, just to wrap up because there was a bunch of stuff we want to talk about. I think the testing has gotten really good. So they have these awesome little kits. Put it in your nose. My kid can go back to school the next day. And I think that’s that’s been a major advance. And I like that technology because it’s useful not just against the coronavirus, but there’s actually a lot of areas of infectious disease that have benefited from the last two years of dedicated research into these areas that’ll make hopefully for our kids and our kids’ kids an easier world to navigate with less pathogens.

Harry Glorikian: Yeah, I mean, I’ve been I’ve been talking about distributed diagnostics for, I feel like 15 years and it took the coronavirus to sort of help move the ball forward in an interesting way. So I hope it doesn’t die. I hope it continues to be…. But do you see an identifiable end to the pandemic or do you just simply, you know, settle gradually from an emergency to something more of a normal, it’s becoming endemic in the society, and public health just sort of manages it like we do the flu.

Jacob Glanville: Yeah. So here’s the way to think about it. The bad news and the good news. The bad news is, yeah, it’s definitely not going away. And like, really, we all knew this six months into it. The thing is so infectious, you saw how quickly it went from first off out of Wuhan to the world. Then you saw Delta, how quickly that got out of India to the world. And then with Omicron, you saw within a couple of weeks of South Africa reporting it, it was everywhere. It’s so infectious that it’s hard to reach a sufficient, even if you had a vaccine that would provide sterilizing immunity, you probably have to get 95 percent of people to take it to protect it. Above 80 is good, but you’d really have to be above 95 and you’d have to have better surveillance networks. It’s not inconceivable to stop the virus. China has actually done pretty astonishingly good job, but they had to apply super draconian measures. And everywhere, everyone everywhere would have to apply those to potentially stamp the thing out. And that and realistically, that’s not going to happen, and that means that the virus is here to stay.

Jacob Glanville: The good news is that it’s not going to be like it was over the last two years. We have a lot of vaccines and good ones that are being administered. You also have natural immunity or natural infection induced immunity. People didn’t really want to talk about it in the last year and a half because they were worried, if you heard a natural immunity can provide protection, that people would just throw up their hands and be like, “Well, just let me get infected.” And that would cause a crisis of hospitals. But the reality is there are some countries like Guatemala just don’t have enough vaccine, and there’s people who aren’t going to get vaccinated. And so as the thing infects everyone, that’s going to provide an additional layer of repeat infection that gives rise to some population-level immunity that boosts people who are vaccinated, and that also helps people who weren’t vaccinated. It gives them a level of immunity. Although again, this virus, you do not want to get it if you can avoid it.

Harry Glorikian: Yeah, I was going to say, I mean, I’ve seen people that have have even, you know, my friend’s son got double vaccinated and ended up with pericarditis, right? So, you know, you don’t know how you’re going to react to it when if you if you happen to get it. So, you know, my advice to people is like, if you can, if you can avoid it, that’s a good place to be.

Jacob Glanville: Yeah. And so that’s where we’re going to move into in the future. You’re going to have a population which is increasingly got some established immunity to it. Kids are going to get exposed early. Hopefully, we’ll have vaccines for kids, but otherwise they’re going to be exposed early and then repeatedly being exposed to it will provide some level of immune protection. And that means that that plus the rapid testing technologies, means that we can move back to a semblance of normal. But with this being an endemic virus now. We’ve lived with other endemic viruses before, you know, HIV never went away. We still have it. We have tuberculosis, we have multidrug resistant bacteria, we have the flu and we find ways to make the medical crisis manageable through vaccination and treatments so that when you get sick, there’s something.

Jacob Glanville: That it’s not creating a crisis with the hospital centers. That’s where we’re going to be with the coronavirus. The the hope is that while people said, “Oh well, Omicron looks more mild, great. The virus is evolving to be more mild.” You cannot count on that. Viruses do not naturally evolve to get milder. What happened was it shifts randomly. It can get lucky. They just get more transmissible. That’s all the virus selects for. It happened to be this one’s more mild. If we’re lucky, that means the children of this one will tend to be more mild, but it could also go the other way. And so we just need to keep these…. That’s what you’re going to experience over the next five, 10 years. It’s going to be more rapid testing and surveillance, which to your point about this, I think that’s what’s actually going to keep that alive and expand it is that that’s going to be a part of life vaccinations and monitoring and better treatments. And that’s the life we’re going to live with and kids are going to grow up in this period, it’s like, that’s what they’ve always known like. We’ve grown used to flu like we’ve grown, used to. HIV is just part of life.

Harry Glorikian: Yeah, I’m hoping that this also, though, encourages sort of global sequencing capability so that we can keep an eye out not just for this, but for anything that’s on the horizon so that we can react to it, you know, as quickly or even faster than we did for this one.

Jacob Glanville: They have this really cool tech that I’ve starting to see. I heard about it before the coronavirus pandemic, but I’ve started to see it used quite widely. And that is RNA sequencing or viral sequencing of sewage systems. It’s a really cool technique where you can test. It’s a way of testing like a citywide level, the prevalence, the the abundance of the coronavirus. But but you can use that technology for any pathogen. And so they’re setting this up on a city by city basis. You learn early before people are even showing up at hospitals. You could start learning “Oh, this virus is starting to appear in the sewage. Therefore, it’s in the city.” And that technology, you could start testing for a whole panel of pathogens quickly, and it gives critical early guidance on disaster response or early response measures and contact tracing. So things like that, things like rapid, there are these cool new rapid sequencing technologies that are available. I do see see a very strong place for them early. I mean, that’s it was really contact tracing and low tech testing that kept Ebola in Africa. And I think we have abundant tools like that available globally, especially around people in transit and people in local communities. That’s that’s useful for coronavirus suppression. And like the flu, we have barely had the flu in last two years, and that’s partially because of all these measures. I’m actually hoping that with really good testing, really good sequencing and contact tracing measures, that gives us an advantage over all pathogens.

Harry Glorikian: Yeah, I just don’t want to be the guy having to go get the sample from the sewage just so you know.

Jacob Glanville: Fair enough. Yeah.

Harry Glorikian: So, so the last time we, you know you were on the show like it was all about Distributed Bio, which used computational tools and discovery and development to for therapeutic antibodies, right? So you were working on a universal vaccine for humans and pigs, and you were hoping you might find a treatment for COVID-19. You sold that company to Charles River in 2021. Bring us up to date. Tell us the story here.

Jacob Glanville: Sure. So, yeah, the history of Distributed Bio was that we were taking advantage of advances in computational immunology and high throughput sequencing, various high throughput assays, which are super useful at analyzing the immune system, which is a very complicated system. So getting a lot of data out is good and in particular, using these to use the immune system as a system for generating drugs, so antibody therapeutics to discover them and engineer them. Using these computational methods that enable Distributed Bio to, we ended up servicing 78 different antibody discovery and optimization contracts for 60 companies. We built part of the generation of new drugs that are coming online over the next few years without taking on venture capital. Because we were profitable the whole time from that service and that I used some of those resources to pour into these internal research campaigns for things that I thought were really cool technologies that were would be too awesome to offer as a service contract, but also too risky. I needed to de-risk them. And so when we worked with Charles River, they were very interested in our service platform and our service business. And they I said, Well, look, I have these things that are near and dear to my heart I’ve been working on. I literally like like shovel pig manure in my own vivarium to go do some testing on this broad spectrum vaccine tech. And they said, Jake, that’s great. We would just want the service business. In fact, our policy is we don’t want to have any program internal and Charles River that would be a potential, a competitive therapeutic or vaccine program, to any one of our clients. We want to service the world. And so you can spin those out and have them independently.

Jacob Glanville: And so that’s what happened at the end of, yeah, it was actually the last day of 2020, December 31st, 2020, and we did the announcement a few days later. In January, we separated the service business, which was the Distributed Bio that Charles River acquired. And that’s that business is still super active, and they’re generating antibodies for companies around the world. And we spun out the therapeutic portfolio of the broad spectrum or universal vaccines and a series of other typically broad spectrum focused medicines like a universal antivenom, broad spectrum anti-infective against a couple of other disease areas that are important, into Centivax. And so that’s what Centivax is. We spent the last year, basically, you know, with a new entity, we were working on our broad spectrum vaccine technology, which you’re going to be hearing a lot about from us over the next couple of years for obvious reasons. Our main program was flu that I was working on from 2012 on. And we have a broad spectrum, our universal flu shot. Now we’re obviously applying our technology now to the coronavirus. And also we’re working on HIV.

Jacob Glanville: Then we have these other programs, including, as you alluded to, the CoV-2. So we made an antibody that could act as an injectable treatment for SARS-CoV-2. That’s gone through manufacturing. We went up to the in the IND process with the FDA. We’re on hold right now with that one because of Omicron. So they basically sent out a an announcement saying, Look, everybody who if you’re making therapies, if they don’t hit Omicron specifically, we are going to pause the clinical development. So we were supposed to go into humans at the beginning of January. But right now we’re looking for a partner. We have additional molecules internally or we’d look for a partner that we’re going to create a cocktail with because we we do best in class on a whole bunch of other variants. But like most of the other antibodies, we got hit with Omicron, so that’s where that one is sitting. It also just frankly reinvigorated our point where like, look, the broad spectrum vaccines are ultimately what needs to happen here because the best antibodies can be hit by a jump. Omicron was a big jump. We saw how rapid this thing was mutating and suddenly jumped like crazy and then it escaped our antibody. And so our vaccine technology is specifically designed to address problems like that. So we’re kind of going all in on it right now as we move forward.

Harry Glorikian: Yeah, because I was, you know, looking at the website and it’s interesting because, you know, the language for Centivax and the language for Distributed Bio, like computational antibody engineering, right? So they they sound very similar. But you know, if I got it correctly, it sounds like the services business is what got shunted off and then the therapeutic business where you’re creating products you sort of kept. Did you keep some of the people or how did you, you know…

Jacob Glanville: Very few. So we had a couple of people that came over. But part of the acquisition or is it like, OK, you can go take this stuff, but we want you to build largely a new team because because we need an operating business, because they are acquiring it for the business. And if I went and like, did my little Pied Piper whistle and all my people came with me, then they wouldn’t have an operating business, which totally makes sense. So and it actually worked out because therapeutics, going into clinic is a fundamentally different type of business than running lots of antibody discovery. So at Distributed Bio, I had a lot of bioengineers and a team of there was a lot of younger scientists because we just need lots of people to run lots of programs. And then there’s a hierarchy of more senior leadership. Whereas Centivax is a therapeutics company, it’s a vaccine company. And so we have less people. There are 15 employees right now and a portfolio of things that we’re focusing on entirely and IP. And my team is much more senior because what I wanted to do is cherry pick my favorite people I worked with for the last 15 years to have a lot of experience of bringing medicines into clinic and driving them to successful conclusion. And so that’s largely a different team. Sawsen Youssef, who is my chief science officer at D Bio, she came with so. And we negotiated hard for that. So she’s with me at Centivax. Dave Tsao, he joined in the last year at D Bio, but he he joined with the idea he was going to move on to Centivax. So that was expected and otherwise the whole team was generated, we were building up Centivax so that we’d have an independent company. So we pulled them together over the last two years and right at the spin out, we had people ready to just jump in and continue work. And so that’s the team we have now.

Harry Glorikian: Now, you know, one of the things we talked about, you know, in our last talk was the influenza, you know, vaccine against influenza. Where are you with that? Because I think I remember you saying 2025 was when you thought that you might have something.

Jacob Glanville: We might be off by a year, but we got the results back. So we have some pretty astonishing results. We got back on live challenge studies here in the United States. So I think at the time we were talking up up until then, all the studies we’d run on that technology, we’re running the vivarium, the animal facility that we produced in Guatemala. So I run that in partnership with the University of San Carlos, I’m an affiliate professor down there, and it gave me the ability to do rapid iteration cycles on live challenges, or not live challenges, but immunizations in live organisms.

Harry Glorikian: And I think it was ferrets and pigs.

Jacob Glanville: That’s right. So the studies up here, ferrets? Yeah, you’ve got a great memory. So yeah, so what happened was the Gates Foundation. We won this Grand Challenge in the Pandemic Threat Award, and the Gates Foundation gave us money to go

Speaker2: Run the studies. They’re like, look, we want you to run live challenge studies, which is where you go, spray the pigs and the ferrets in the nose with virus to see if they get sick. It’s the ultimate test, and I can never run that in Guatemala because I can never bring virus down there, and my facility wasn’t bio contained enough to do it safely. Whereas up here we’re working with the University of Georgia has this guy named Ted Ross, like everybody in the vaccine space, knows he’s an expert at running these kinds of studies, and so we ran the ferrets with him. And then we have Konstantinos Caracas, who used to work with Ted Ross, and now he’s a professor at Auburn University. He does a bunch of these pig challenge models. And so we ran those studies. Those were cooking for last year and then into all most of last year and they’re long studies because you’re giving vaccinations. And then after that, you’re giving exposing the animals to virus and letting them recover and checking to see, you know, the ultimate question, like, did it protect them from getting sick? Did it protect them from producing the virus in the lungs and the trachea and in the nose and stuff? And the data looks absolutely outstanding. So we’re preparing a paper on it right now. We’re looking now into manufacturing it to go into clinical trials so that we can go develop a broad spectrum vaccine for flu for humans. We’re also going into the pig market because it’s a $180 million a year market in veterinary space and it’s the the same sets of proteins we’d be using. So it’s kind of a free additional line of revenue, which in general, I always like to work on a veterinary relevant application of the same therapeutic when you can, because it makes sure that your drug works because like nobody really cares about a mouse, the mouse is very different than a person, whereas like some farmer cares about that pig, so your drug better work. And you make money earlier, it’s a great system. Yeah, so we’re pushing on that. And then for the same reasons, you know, we’ve been slow cooking the same technology on HIV for the last year and a half, and it’s looking very promising so far. Although it’s early.

Jacob Glanville: I had not activated it against the coronavirus for the first first year and a half. I didn’t because I thought, Eh, this virus is it’s got a proofreading mechanism, so it shouldn’t mutate that fast. And B, there are these other technologies that were just blazing forward so fast with the RNA tech. I just said, you know, I want to see how they do. There’s like 180 companies working on vaccines. Let’s see how they do before I go dive in there. They may not need my technology, but then in the last few months, we’ve seen the rise of Delta and then Omicron and a whole bunch of other super-mutated versions. And that absolutely needs my technology because the current vaccines are having real problems keeping up with the new mutant versions. So we are running the accelerated studies right now using my same vaccine platform on the coronavirus as we move the flu program in first. The coronavirus is actually moves pretty fast because we can benefit from a lot of the legwork we did already in the pigs and ferrets for the flu program and then the the HIV program, the that one, I’m a little more hesitant on when it will be ready. It’s a big, first off, it’s a big lift. So I want to have really, really good data before I start trotting around being like, “Hey, you remember that HIV problem? Yeah, fixed it.” You know, I can’t say that yet, so I need to see the data. But also but like technically, as a bioengineer the HIV proteins are tricky. They tend to fall apart. And so we’re doing a number of things to try to figure out how do you make a vaccine and actually make it practical to deliver it? And we haven’t solved that yet, and I don’t have a solved engineering solution. I always like double my timelines until because because you just don’t know how annoying that little path is going to be. It could be easily solved or it could be worse than you think. And so that’s sort of our our we’re going to get it working. It’s just going to take some time to make sure I have it nailed on how we deliver the HIV proteins.

Harry Glorikian: Yeah. And when you think about HIV, I actually, you know, I think it’s becoming, you know, if you look at. The populations where coronavirus is mutating, it’s immunocompromised HIV patients, right? So if we could solve one problem, you might. I don’t want to say you could kill two birds with one stone, but you might actually solve another, you know, problem that that maybe hadn’t been as big of a problem before coronavirus and now is becoming a problem.

[musical interlude]

Harry Glorikian: Let’s pause the conversation for a minute to talk about one small but important thing you can do, to help keep the podcast going. And that’s leave a rating and a review for the show on Apple Podcasts.

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It’ll only take a minute, but you’ll be doing a lot to help other listeners discover the show.

And one more thing. If you like the interviews we do here on the show I know you’ll like my new book, The Future YouHow Artificial Intelligence Can Help You Get Healthier, Stress Less, and Live Longer.

It’s a friendly and accessible tour of all the ways today’s information technologies are helping us diagnose diseases faster, treat them more precisely, and create personalized diet and exercise programs to prevent them in the first place.

The book is now available in print and ebook formats. Just go to Amazon or Barnes & Noble and search for The Future You by Harry Glorikian.

And now, back to the show.

[musical interlude]

Harry Glorikian: So, but, when you’re working on these things, do you think there’s enough government and private sector support for some of the other things or is coronavirus sort of, you know, sucking all the oxygen out of the room?

Jacob Glanville: Yeah, so that’s a great question. Yeah, I spent a lot of time thinking about this. So the. You know, we have I have these other programs, right, so that I actually I inherited a whole portfolio, I have more stuff than I know what to do with it. Our decision was first off, because we had amazing data on the time, and this is the time where everyone says, Look, we need to, this is ridiculous. We need better, more broad spectrum vaccines and we have the IP that works. We’re focusing on that. These other programs, like at least with the vaccines for flu and HIV, there’s resources out there. Paradoxically, like we were told by some government agencies, you know, it’s actually easier to apply for flu money than COV-2 money because it’s so so like tied up and and policied out already or the bets have already been placed. With HIV, we actually have, basically with HIV I’m waiting for the first of these critical animal studies that will tell me when I can start waving the flag and saying, Hey, look, we have something exciting here and I can run those studies internally and they don’t cost me that much. So I’m just waiting to make sure I have a pie to bake before I start yelling around and saying I need an oven. For the other programs it’s a mix. I think it’s definitely the case that, like one of the things we inherited is a cancer program, and four years ago, venture capital groups. I would show them my vaccine technology. They would listen to it. I’m like, Look, hi guys. You know, I want to be humble here, but like this will solve all of those mutating viruses that we’ve struggled with. How would you like it? We could contemplate a world without some of the pathogens that we’ve lived with since the beginning of time. And they’re like, “Sweet. Can you apply it to cancer?” Because four years ago, all they all wanted cancer drugs that was really hot. Well, the thing flipped. That’s the kind of amazing because it’s good timing. I’ve worked on this thing for nine years. I show up and then suddenly I still thought I was going to have to fight this thing uphill. I have a cancer assets that I could use, talking with venture capital groups, and like much to my delight, they’re like, “You know what, actually the vaccine thing is what we care about.” So finally, it’s like, become popular. I feel like a high school kid who like, went through puberty and suddenly I’m popular at the school ball or something. I’m like, “Oh, sweet, you like this now? This is great because this is what I’m really good at.”

Harry Glorikian: Timing is everything, man. I mean, you know, if you’re just off the mark, people don’t see it. So, but you know, I think if I was reading correctly, you’re also working on a bunch of antibodies against bacteria like Staphylococcus, Pseudomonas. You know, these are all bacteria that that seem to have evolved some resistance to the classic antibiotics. So is is, you know, why is your platform good at targeting these organisms and where are you at with that sort of thing?

Jacob Glanville: Sure. So the unifying concept of the company is like, we have this tagline “Smash the mutants.” Yeah, the principle is we focus on areas of medicine where mutations are the thing that causes a problem of effective treatment. And so for our vaccines, we have this broad spectrum spectrum vaccine technology. For areas like cancer or bacteria or snake venom, there’s also a problem of mutation, and we in many cases, we use broadly neutralizing antibodies to address them. So with the thing you brought up, which is the multidrug resistant bacteria, there, we’re doing something that honestly I think other groups should have done eight years ago. But the there are there’s this impending wave of doom of a bunch of new multidrug resistant bacteria. It’s pretty easy for bacteria like staph and pseudomonas, the kind of nasty things that get in a wound to develop resistance to the antibiotics. Like within a year of creating a new antibiotic he bacteria has got, there’s some new variant out there that’s resistant to it, and within 10 years, that becomes the dominant variant if that antibiotic is used at hospitals at any frequency, and it’s they’re able to do this because there’s a lot of genetic diversity in the population of the bacteria. They they have a half, every 30 minutes, they’re making a new copy of a bacteria in some cases. And every time they do that, there’s a chance of a mutant. So there’s lots of mutant bacteria out there in the world. And so as soon as you start using an antibiotic, whatever one of those bacteria that’s resistant to it is suddenly going to gain a lot of favor. And it’s really easy for them to gain antibiotic resistant because all they need to do is have one mutation in one gene to block the one pathway for that one antibiotic. There were efforts to use antibodies as therapies against multidrug resistant bacteria 10 years ago, I was involved in some of them. But at the time, the feeling was that manufacturers would only want to produce one antibody. And the FDA would only want to prove one antibody. So you need to do the job with one antibody, which is super stupid, because, we knew this back then, bacteria are not, they’re not one-trick ponies. Staph is an amazing engine of war. It’s releasing multiple different toxins. Here’s one to go knock out your B cells. Here’s one to knock out your T-cells. This one’s going to trip up your, your neutrophils. And so forth. And so we try to make one antibody block one of these things, the other, the other toxins would just do their job and mess you up. And so what we’re doing is we’re going back and saying, OK, first off, let’s get some broadly neutralizing antibodies that can hit multiple toxins at the same family. And second, let’s get a couple different antibodies to go after those different, those different toxin classes in parallel, and so we’re creating a multivalent solution to go after multiple different toxins all at once. That’s really how the body defends itself, and that’s an effective drug solution. It uses broadly neutralizing antibodies. So we hit these shared sites that are found between the toxin flavors or variants, but it’s otherwise it’s a practical approach. I think our technology helps us go after those broadly neutralizing sites, and it also enables us to engineer the antibodies so that they don’t require an IV bag, which right now with the coronavirus does. Antibody treatments usually required an IV bag, which means you had to go to an IV infusion center, which means they wouldn’t give it to you because they didn’t really want you going into the hospital with the virus because they had people that honestly were more sick than you already were. What you really want is an injection that could be done at it  Walgreens, or it could be done at home or an outpatient treatment facility. But to do that, you need to engineer your antibody so you can concentrate them like crazy so they can go in a syringe and they need to not be so thick that it’s like toothpaste. They have to have low viscosity so you can inject them. And we are really good at engineering antibodies so they can do an ultra high concentration and low viscosity. And that’s part of the reason why we have partnerships with the Navy and the Army because of our capacity to do this. And then it’s also with the NIH. We’re doing it for our antivenom program. Also, you want something that has no temperature control, can be delivered ultra high concentration and can be shipped around the world, which is really the way I think antibodies should be delivered everywhere. But but certainly in these applications is a great place to start.

Harry Glorikian: So, yeah, but you know, it’s interesting, right? I mean, you’re talking about all these incredible hurdles, right? I mean, you know, people say DARPA-hard, right, these these are not easy, right? So isn’t there an intermediate step so that we can? Yeah, help a bunch of people along the way.

Jacob Glanville: Yeah. Let’s see. Well, I mean, that stuff I just described is done. We like we have a cocktail, which is already a staff is our first, our first bug that we’re going after that’s done with the Naval Medical Research Center. We have a cocktail of antibodies there, concentration engineered and we already completed our concentration engineering technology. We used it actually on our SARS-CoV-2 program. It’s the highest concentration antibody ever produced through GMP at 254  mgs per ml. So we’ve we’ve got that built. We just we just can apply this to antibodies when we want to now. And so we don’t there’s not a set of steps before we can get there. This is just how we produce our drugs.

Jacob Glanville: Now, the the thing that you know, the thing I worry about, which is fair, is it’s like, OK, I actually have more things in the portfolio than than I have time to effectively focus on all of them. So our strategy has been all in on vaccines right now. This is the time for it and we have these programs. Some of them are supported by grants. And so the grant supports some continued development on them. Some of them, we’ve frozen down Some of them we continue because they’re looking super promising and we have grant money like the the universal antivenom. That one is covered by an NIH grant. The Naval Medical Research Center is working with us on the Staph program and we’re running live studies with them. Otherwise, our other programs are mostly being paused right now. This is the beginning of a portfolio later, but right now there’s so much promise in the vaccine technology. I’m like, I’d rather just nail that like crazy. And then we have as we grow, as I contemplate an IPO, I’m going to have a nice, rich portfolio or I have a business development partnership portfolio I can I can engage other groups with. And that’s kind of how I “Focus on focus” and prioritize these things.

Harry Glorikian: Yeah, because when you were talking about the the antivenom, I was like, OK, I don’t know much about chemistry of snake venom. That one sort of slipped my purview over time, not been at the top of the list. Maybe if I lived in Arizona or something like that, I might take it a little bit more seriously. But Massachusetts, we don’t have this problem. How does your how does your computational platform help identify like? Is it the same thing that we were just talking about when it, you know, when we come to the, you know, against the bacteria, is it the same approach?

Jacob Glanville: Yeah. So I mean, at heart, everything I’m talking about involves broadly neutralizing antibodies. These are these antibodies that recognize a shared site that either a virus can’t mutate because if it mutates that site, the virus doesn’t work anymore and we just get an antibody to go bind that site. It’s the Achilles heel of the virus, or it’s a shared site between different evolved versions of like a bacteria toxin that it can’t change that site because that’s the site that’s necessary for the the toxin to do its job. If we get one antibody against it, it’ll block all the toxins of that class. Or again, snake venom. We have a broadly neutralizing antibody that hits like the one shared site on the neurotoxins of all snakes. Then you have a single antibody that could act as a universal basis of getting rid of neurotoxin against all snakes, so therefore universal antivenom. So that’s the power of broadly neutralizing antibodies. And then our technology platforms are either vaccines which are engineered to make you produce them. So we give you actually collections of proteins and you produce those broadly neutralizing antibodies or on the antibody side, we make them in the laboratory And then we deliver them to the patient. But that’s the that’s the central principle.

Harry Glorikian: It’s interesting. I wouldn’t have. Again, not knowing anything about snake venom, I’m like, is there is there a universal site across all venoms?

Jacob Glanville: There is? Yeah, it’s actually pretty, this is a cool project, so it’s a side project that I lov so much. Som there are five hundred and fifty venomous snakes that cause risk of death or or limb loss in humans, and it’s more than you think. 100,000 people die every year, and another 300,000 or more get permanently injured. 550 different snakes and each snake is injecting like 10 to 70 different proteins in their venom. So it’s a very complex mix, which seems insane. If you look at that, you’re like, How are you ever going to make a universal antivenom? But if you look at it, the the snake venom, actually, if you take all those sequences of all the different toxins and you analyze them, they actually collapse down to 10 families of toxins. And of those, there’s really only four that really matter. The other six, it’s going to hurt. But you know, like, suck it up and walk it off, you’ll be OK. If it’s a neurotoxin that’s going to stop your heart and stop your lungs and cause you to go rigid and die, that one’s no bueno. You have a phospholipase that causes a whole bunch of other tissue problems. Serene protease metallo-proteins. These are these are the things that are going to tear you up. That’s the reason you’re you have to amputate. That’s the reason you die.

Jacob Glanville: And so because all the animals use the same, all these snakes use those same four toxins. If you can make an antibody against each one of those four, really four antibodies would be a universal antivenom. Which gets to your question. Ok, but are they concerned enough that you could get a single antibody? And the answer is surprisingly is yes. And here’s the reason. Ask yourself there’s 550 snakes. These things are eating, they’re eating birds, they’re eating little mice, they’re eating fish, you know, whatever. Like all these different animals, they’re all very diverse. How is it that they’re neurotoxin works on all these very diverse, diverse, different species? And the reason is this it’s pretty cool. The neurotoxin binds to the nicotinic acetylcholine receptor. If you line that up the sequences, it is almost invariant all the way out to fish. And this is even a pretty conserved receptor, even more primitive creatures than fish. So this thing has not changed, particularly the sight of the nicotinic interaction since the dawn of time, right? Evolution hasn’t changed the site, and that’s because the and this is true for many neurotransmitter mediated brain genes, the ones that interact with a molecule that’s providing signaling that those neuron networking, that’s like the wiring in your house for the internet, it hasn’t changed since the beginning. So they haven’t been able to evolve it. And the neurotoxin in these snakes all binds that exact same site, which means that neurotoxin works on all species. That also means that the snake venom, even though the snakes have evolved elsewhere, they can’t. They can’t change that site that interacts with that gene that’s never changed or their their their venom. Their drug won’t work on all these species, and we’ve found an antibody that docks directly into that site and therefore it hits all the venoms.

Jacob Glanville: And where we got it from was a guy named Tim Friede, who spent 17 years and nine months self immunizing with escalating doses, 700 self injections of snake venom from Cobras, Taipans, Mambas, western diamondback, Mojave Crate. The list can go on, and he has meticulous records. He built up hyper immunity against the snakes to the point that he had received 202 bites from many of these snakes and survived snake bites that would kill a horse. And I reached out to him in 2017 because I geard what he did, and I built a technology that made it easy to go harvest the DNA sequences of the antibodies you’re producing. And I wanted to test it on something. And so I found this. I was looking for someone who like I was looking for a clumsy snake researcher who’d maybe been bit three times. And instead, I found I found out about this guy and I was like, I got to test his blood. And so I said, Look, I think you may have done something amazing because you kept changing the snakes over and over again for almost 18 years. I think you selected for these broadly neutralizing antibodies, and I’d like to find them. And we started collaborating. And sure enough, we found the collection of these remarkable antibodies, and we know that he’s got them in him because Tim isn’t dead and he should be if he doesn’t have broadly neutralizing antibodies. And so that he’s the real cool. I mean, computational stuff helps us harvest them out and do some analysis. But the real the real magic for that program is Tim Friede.

Harry Glorikian: Yeah. “Honey, honey. Don’t worry, I’m just it’s just a bite. Nothing’s going to happen. It’s only a king cobra. Like, we’ll survive this. It’ll be fine.” He’s the guy you want walking in front of you through the jungle first. So well, that that’s interesting. Well, I’m you know, this is why I do this show, right? I learn something every day. So but in the big picture, like, you know, COVID-19 seems to have like really changed the game in this whole space, right? I mean, it’s all sorts of attention for therapies and it’s bleeding into, like you said, you know, maybe infectious disease, including autoantibodies, I mean. You know, but here’s the question is, is it is it getting easier to do the research in this area than it was Pre-Covid, is there more interest from partners and funders? You know, how is the technology itself improving? I mean. All of this, I think in a lot of areas that I’ve seen is caused forward thrust of activity, money technology, and so I’m asking you that question is what do you see, is it really helping?

Jacob Glanville: This is a mix, so I would say that. There are a number of technologies that benefited, so certainly rapid testing has gotten way better with respect to therapeutic development. There was a period where,

Jacob Glanville: And to their credit, the FDA did an amazing job during this period of triaging an insane number of incoming requests. And they did it super fast. Like everyone who I’ve ever worked with in this space was like, I cannot believe how responsive the FDA is being right now. And so we’re all worried that that might change back to the old, you know, the more standard way. Pretty soon, we’re hoping that they’re actually this has given rise to an improvement in the the pace. It may not be crisis level pandemic fast, but there might be improvements in terms of the turnaround time with the FDA. And that would benefit drug development. There’s been it spurred a lot of additional exploration into manufacturing platforms, discovery platforms. I think that stuff before and for me personally, it’s I mean, really, it’s the timing is brought on like a golden age of interest in better new vaccines, right? When my technology was right for prime time, which I am excited about. I think those things are good. I think there is also a lot of new research, like a remarkable new research. the whole world was so much of us were attending to these rapid inducible animal models for live challenge against new viruses and the like, these pseudo varion particles and all these cool new technologies that will serve us well as we go after additional pathogens. And there’s like a level of like reluctantly induced immunology fluency and virology fluency among our politicians and our policymakers, which is helpful, I think. And you know, that’ll wear off, but I think over the next five years, I think that’s helpful because, you know, nobody used to know what I did. And now I go into rooms and people like, “Oh, what do you think about the immune imprinting theory of original antigenic sin after receiving a cross vaccine?” And I’m like, “Oh, hi, grandma, how are you doing?” It’s crazy, people have a lot more knowledge of our space now. That’s that’s that’s great. And because I think that really actually helps. The space is complicated. It’s immunology, it’s epidemiology. And so how do you even make people start to have good policy decisions if they don’t have some level of exposure to the concepts? And I think that’s just dramatically changed. The whole world got a master’s degree in infectious disease in the last two years, and that’s a good thing.

Harry Glorikian: Excellent. So you think the glass is half full as opposed to half empty on the future of. Drug development against infectious diseases.

Jacob Glanville: I do. I Actually do. I think we’re actually in the kind of entering the golden age. It seems funny to say that in the middle of a pandemic we can’t seem to squash. But I think this did serve to accelerate infectious disease therapy, vaccines, diagnostics, and I think that’s going to serve us really well because there’s lots of different pathogens out there that have made us. And I think we have encountered this this time in a golden age of biotechnology and I think a lot of tools and realization of interest. So venture capital is suddenly interested in these technologies. Big Pharmas are realizing, Hey, you can make big money from infectious disease, where before I think it had been relegated to the back seat or the big boy cancer and neuro and a couple of others, cardio, we’re sitting up in the front seat and I think that’s changing. And that’s good because like infectious disease is unlike many other diseases that humans have in that you can eradicate. It’s not outside of the question that you could solve the disease forever until the end of time. And that’s exciting, to be able to deal with our in our hands and our in our lifetime, if you can contribute to that.

Jacob Glanville: Now I want to be blunt, it hasn’t happened that often we’ve gotten really pushed down certain pathogens. We’ve only really succeeded in eradicating through vaccination one, close with a few others, but maybe we’ll have the tools now to actually push farther. Maybe we’ll create that network.

Harry Glorikian: Yeah, no. I mean, I totally. You know, I try to tell people when I’m giving talks like, some things that would have taken another five or 10 years at a minimum have been pulled forward, yeah, because of this dynamic, and, you know, it’s not just in where you are, but like. telemedicine and digital products and all sorts of things that have sort of been thrust forward because of. You know, so I try to look at the silver lining of. I’m sure there are people going, “It still sucks.” I know it sucks, but sometimes you need. A push to move this stuff forward or at least get people to take the right level of risk or chance to to to get something to jump forward.

Jacob Glanville: Yeah. You know. It’s the presence of the crisis has given it a lot of attention and the fact that it’s going to be annoying and frustrating and still dangerous for some years ahead means there’s going to be sustained attention here I. I got to be blunt, I don’t see how they’re going to eradicate it in the near future. I think it’s possible technically but impractical, and that means that there’s going to be a period where this is still going to pose a significant economic burden and annoy people and that that serves to put more. That’s going to drive innovation like we innovate in the squeaky wheel, gets the grease and the coronavirus, and pathogens are a squeaky wheel right now. And I think that is a silver lining here, I think. Beyond the wave of people going through yet another cycle of realizing, hey, this isn’t just going to magically disappear, I think there is a silver lining on the other side of that where people are going to say other coronaviruses around, but it’s manageable now. We don’t have lockdowns anymore. We can live our lives. It’s just something you have to watch out for it. But there are, there are vaccines and we have better ways of detecting and squashing the outbreak. So I think there is going to be a life resembling normal as we remember it, the new normal. I think that is going to emerge. And that’s going to be good for people, but they’re still going to be a pressure here, which we also, we it’s not only good that we’re doing this, we have to do this. Because we have more people on the planet than we’ve ever had before. And they travel much more than they ever had before. It’s the astonishing level of speed that this thing got out of South Africa hit all the major hit all the major airline destinations like within a couple of weeks, the virus was everywhere, and that’s the reality world we live in. So we need these tools as we become a rapidly moving and highly populous planet to be able to protect ourselves. Because otherwise we’re just going to keep running into this and potentially at an accelerated pace compared to even previous generations, where at least they had slow moving boats that would stop the slowdown.

Harry Glorikian: Yeah. I mean, can you imagine if we had this level of travel in the 1918 flu? I mean, that would have been bad. Well, look, I’m I’m an optimist like you’re an optimist, I’m really hoping that all this like makes the positive change and and I’m on the venture side anyway. So I like, you know, I invest in it and, you know, I’m hoping for, you know, a profitable outcome. But at the same time, you know, making a difference in people’s lives and having a positive outcome for, you know, everybody on the planet. So God, it was great to catch up with you again. I mean, it’s only been two years in the world is I don’t think I’ve left this room for two years, but that’s what it feels like.

Jacob Glanville: So we can’t because of Omicron. So but we’ll be getting out of these rooms soon. That’s the point I want to make.

Harry Glorikian: Yeah, no, no. And believe me, nobody is looking forward to it more than I am. So I think the extrovert has become an introvert over time. So it was great to talk to you. And you know, I look forward to staying in touch and seeing the evolution of Centivax.

Jacob Glanville: Right on. Well, thanks again for having me on, and it’s always fun to talk.

Harry Glorikian: Thanks.

Harry Glorikian: That’s it for this week’s episode.

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