[Second of 2 parts]
Jacob Glanville, PhD, CEO and president of Centivax, discussed his company’s focus on COVID-19, timing of future clinical trials, and plans to pursue Series A capital in an exclusive interview with GEN Edge. Read Part I here.
In Part II of this interview, Glanville discusses why Centivax waited to apply its platform to COVID-19; the company’s $10 million seed financing and future financing plans; and how soon its vaccines could reach the market.
(This interview has been lightly edited for length and clarity.)
GEN Edge: Why did Centivax wait on applying the broad-spectrum platform to COVID-19?
Glanville: Part of the waiting was I didn’t have the data to execute my technology. The other part, honestly, was I wasn’t sure what would be needed. In the beginning of the coronavirus outbreak, RNA technology moved very swiftly, and it wasn’t clear that this thing was going to dramatically enhance its infectivity profile with each new variant of concern. It’s been astonishing how quickly the coronavirus has adapted to human populations, and grown more transmissible, more infectious and mutated quite quickly under some circumstances, like the big jump that happened with Omicron.
The other part of the waiting was, I wanted to make sure that we were actually needed for coronavirus. Now, of course, the answer is, yes—we are stuck in that world where we’re going to have to make new vaccines and get repeat boosters. Now, we have the data, so it’s a perfect time for us to address that problem as well.
GEN Edge: What attracted Centivax to its partners for the $10-million seed funding? How will you use the proceeds?
Glanville: We just received funding from NFX, which is a dynamite investing group that are professionals at polishing up companies and driving them forward. They co-invested with the Global Health Investment Corporation, which is a government-affiliated body that has the mission of ensuring global health security.
The $10 million we raised is enabling us to initiate the manufacturing steps for that as a prerequisite for human clinical trials, so creating the MCB [master cell bank] cell lines as part of the GMP process. That’s where the influenza program is. This stuff takes time. We need to manufacture it. We need to do safety and toxicity studies, and then we can start our clinical trials. We are contemplating a Phase Ia/Ib, where the “Ib” would involve a live challenge, which you can do in influenza. That’s attractive for our purposes, because we want to be able to establish breadth and pursue that broad label. The challenge enables us to pick viruses that are the ones circulating, to be able to test more diversity quickly.
GEN Edge: How soon does Centivax plan to launch that Phase Ia/Ib trial for influenza? And how soon for COVID and HIV?
You always get bitten for making these estimates! But when I look at the GANTT chart, we’re talking about roughly two years to be able to start the Phase I study for the flu. We may be able to be beat that. But I’d rather give a more conservative estimate than not. The study takes about six months to complete the Phase Ia. The Phase Ib is a little less than that.
Glanville: The HIV and coronavirus trials are going to take at least another year beyond that, because we’re still in the process of optimizing the composition and the formulation. We’re also exploring, putting our technology onto RNA—so far, it’s been protein-based. But we think that there’s some advantages using the RNA platform, and we want to validate that for coronavirus in particular, because it’s already a standard platform. We think that that is a good choice for us to use the RNA technology for that purpose.
GEN Edge: How did you connect with NFX and the Global Health Investment Corp.?
Glanville: We started the company in 2021. Because of our unusual history, we had an unusually good amount of traction. We had the Gates Foundation Grand Challenge Award. We also were featured in a Netflix documentary series “Pandemic: How to Prevent an Outbreak,” that spookily came out right when the pandemic was starting.
During that period, I sold my first company to Charles River Laboratories. BARDA [Biomedical Advanced Research and Development Authority] was familiar with our work and had been following it with interest for some years. We were supported by Cooperative Research and Development Agreements (CRADAs) with the U.S. Army Medical Research Institute of Infectious Diseases, the Naval Medical Research Center, Walter Reed Army Institute of Research, and other government institutions that that supported our work. I think we had that level of traction where people were aware of us.
In the case of NFX. I was familiar with one of their partners, because at the same time he sold a company to Twist Biosciences. I was also working with Twist on a project. That’s how we got to meet each other. We were both mentioned multiple times in their SEC filings when it went public, and so we remembered each other. We both had a positive impression of each other because we both knew we could get stuff done.
It’s not just good enough to have a very ambitious goal like eradicating pathogens. You have to have people who know how to make it. It needs to make money, or it’s not going to become a reality. And you need to have someone who’s able to execute. And I think we both knew each other could do that. That was the basis of that interaction with GHIC. It came through those government relationships that we had. They became aware of us, and we initiated the conversation, and we were super mission-aligned with them, because what we do is exactly what they care about, which is global health security.
GEN Edge: How long did it take to complete the financing?
Glanville: We were cruising along with a whole bunch of interested parties in February 2022. Then suddenly, bombs started dropping over Ukraine and the oxygen got sucked out of the room. Everyone got freaked out by the economy, and we actually pivoted our strategy and refocused on what we were working on. It took us longer than normal.
We probably spent eight months going through the process with NFX. It was pretty fast. When we managed to connect with them—I don’t remember exactly, but I think it was three or four months to complete everything.
GEN Edge: How did Centivax pivot following the Ukraine war?
Glanville: Initially, there were groups that were interested in investing in us when we were in a bubble and the economy was overinflated. We were in discussions with groups who were like, ‘Jake, you should be raising way more money. You should be raising $100 million.’ I said, ‘I don’t want $100 million. I want less than that.’ But we were like, ‘Alright.’ If there’s crazy money available, we would just go advance all three programs into the clinic and do them all, and more money helps. It helps you accelerate more programs, more shots on goal. You get them into the clinic faster.
We altered that strategy when people began freaking out about the economy. We pivoted to, what did we actually need? The critical thing we needed was to enter manufacturing. It’s a key inflection point, and it’s also just an important thing. Our technology is a multi-valent vaccine: It provides broad-spectrum vaccine tech protection, and you don’t have to change it every year. That’s a huge advantage over influenza and the current coronavirus plan. But you have to produce more components there.
There are already blockbuster technologies that do this. We have Gardasil and Prevnar, and others. But there’s an upfront manufacturing burden to prove that you can do that. We wanted to start building those cell lines so that we were already in that manufacturing process. That sets us up to remove one of the technical questions that would come up as we move forward towards Phase I clinical studies.
GEN Edge: You mentioned the downturn in the market being a factor. How much has COVID fatigue been an issue with investors?
Glanville: I think it’s worked the opposite for us. I was interested in this work since 2012. When I was going around talking with investors in 2014 and 2017, they didn’t care about vaccines back then, right? There was not a full appreciation of the importance and the financial potential of the vaccine market. I’d talk to them about it, and they’d say, ‘Okay, can you apply it to cancer?’ And I’m like, ‘No. The killer app here is to eradicate pathogens that have harassed us since the beginning of time, so that every generation that comes after is protected like that. That’s the killer app!’
The coronavirus pandemic has accelerated the appreciation, interest, and investment in vaccine technology, not just for the coronavirus, but for other pathogens as well. I think [COVID] has been a net positive. It’s also clearly advanced a number of technologies – we would not be talking about RNA technology to the extent that we are, if it were not for the pandemic. That has helped us.
I also think that it has helped create networks. It was unthinkable to have a global capacity to deliver RNA at low, low temperatures throughout the world until the pandemic, where we demonstrated we could do so. There’s increasing manufacturing infrastructure being built everywhere. Still, so far I was hedging my bet. A protein-based vaccine is still easier to manufacture globally than RNA. But that’s getting increasingly less restrictive. So, I think there’s advantages financially for fundraising, and also for the infrastructure and technological developments in the space.
We’re in the vaccine golden age right now!
GEN Edge: How much of a runway does the seed financing give Centivax?
Glanville: It gives us 18 months of runway, which is great because we have about six months of really critical milestone experiments. One is entering the manufacturing phase with the cell line development. But we’re looking at additional studies on imprinting because we think that’s a key advantage of our technology. We’re also looking at transmission studies, which are normally neglected by vaccines. We think that we get a 99-99.9% reduction in virus in the lungs of the trachea of these pigs, and reduction in the ferrets.
We believe that that level of reduction is, like, undetectable virus in most places tested in the pigs. We think that means they’re also no longer able to transmit the virus. We’re set up to test that. So these experiments are also executing in the next six months.
We have more runway than we need, because it enables us to do extra things. But it also means that we’re going to be pursuing a Series A in relatively short order. Once we’re integrating into this online development, I don’t want to have to pause that; I want to be able to ramp this as quickly as possible. The world needs these medicines, and I want to complete manufacturing and initiate the clinical settings as quickly as possible.
GEN Edge: How soon are you looking at a Series A round?
Glanville: It would be like six months from now. As a general principle for running companies and building them smoothly, you want to be able to make sure that you always have a long tail of runway behind when you raise the next financing. We’re ready for that next step, and that next investment to go push us into the major inflection point. We’re looking to raise around $50 million.
GEN Edge: What’s the current headcount for Centivax? And how much will that grow over the coming year?
Glanville: We currently have 14 team members. We really only need one extra person right now, and we’re looking for them. There’s a couple of extra people following this year that we need. We’re looking for a chief medical officer, which is important. On our board is [Anixa Biosciences Chief Development Officer] Pamela Garzone [PhD], who’s brought over 50 INDs and four BLAs successfully through the regulatory process. That’s an immense background. But we also want a full-time chief medical officer in house as we look to the Phase I results.
Then the next step naturally would be an IPO, so a chief financial officer (CFO) becomes important at that point.
The other thing that happens after Phase I for us is that because we work on vaccines that have broad-spectrum seasonal and pandemic protection for influenza, there are government funds that potentially could sponsor the Phase II and Phase III trials. There’s no diluted funding that could cover Phase II and Phase III. Depending on whether we access that funding, we will go execute those studies using an adaptive trial design in both hemispheres—basically, hitting all the major continents.
That’s another advantage of our technology: You can work in the Northern and Southern hemisphere, in which case we would potentially delay an IPO [initial public offering] a bit for that reason, because we already have the ramp. Otherwise, we would execute the IPO at that point. We need a CFO to accomplish that.
GEN Edge: Given that these are pathogens that you’re looking at in the broad-spectrum vaccine, how much will Centivax rely more on government funding to at least get the vaccines developed and distributed?
Glanville: It’s been great, I think that is an area that’s helpful to Centivax is that we’re super mission aligned with government organizations that are interested in infectious disease. That’s why the Navy, the Army, NIH and NIMBL (National Institute for Innovation in Manufacturing Biopharmaceuticals), and all these other groups have supported us.
We work in a space where there’s three levels of benefit. One is the population. It would be great to have a flu shot where you don’t get sick. It would be great to have a coronavirus vaccine that not just reduces your chances of going to the hospital, but stops you from getting sick in the first place.
Second, there’s a global economy in health security issues. You want to not have new pandemics pop up. Obviously, COVID was immensely disrupting. I would like to not have another one in my lifetime, but statistics tell me that it is quite likely we’ll have another significant outbreak of some pathogen within my lifetime, and we would like to mitigate that.
The third application is the military application. There’s a concern for militaries that you have something like Coronavirus, or something more severe that could interfere with military function, and so they want to make a broad-spectrum. Vaccines are important for them for protecting them from naturally source things or the possibility of dual-use technology, where some bad guy creates a problematic pathogen. The beauty of broad-spectrum vaccines is that the bad guy cannot mutate the conserved site. The whole point is, nature does not allow you to change that! So even if they try to change other things to make a weapon, a broad-spectrum vaccine would still confer protection against that pathogen they’ve tried to evolve.
GEN Edge: Why is Centivax not applying its broad-spectrum vaccine platform to TB or hepatitis B, the latter generating some two billion cases a year?
Glanville: Not every pathogen needs our technology. Tuberculosis, for example, doesn’t use rapid mutation to avoid the immune system. It hides in cells in our lungs and recreates macrophages. You don’t need us for that. The pathogens where we can help are the ones that are the reason we don’t have working vaccines, and we haven’t managed to suppress or eradicate them—they mutate rapidly. We don’t really need to focus on TB and Hep B, where there’s already a working vaccine, but on coronavirus, HIV, and influenza—next, we will work on malaria.
GEN Edge: How would you sum up Centivax’s goal?
Glanville: We eradicated smallpox in 1980, and that was something that left pockmarks on the face of a pharaoh, and then we killed it, right? And then we stopped doing eradication programs. Part of it is geopolitical; it’s not to do with the quality of the vaccines. But for many pathogens, it is impossible to attempt eradication right now without broad-spectrum vaccines. They focus the immune system on conserved sites, which slows down the mutation rate of the pathogen, so it enables eradication campaigns.
It is my goal to create broad-spectrum vaccines. It is my hope that as a consequence of the pandemic, there’s a new-found geopolitical will to be able to enable eradication campaigns. That’s not going to be until 10 or 15 years out. You have to get these things on the market, and people have to get comfortable with them.
We have the possibility in our lifetimes to create an improvement in health that would have lasting value for a thousand generations that come after. That’s the kind of thing that gets us out of bed in the morning. And we’ve already done it. I have to believe we can do better than the 1970s.
It’s like space flight, where they got us to the moon, and they stopped trying. And now we’re starting again, and I feel like, broad-spectrum vaccines are an opportunity to do this great work, with our company and other great companies that are working on this problem. I think we could be the generation that could eliminate certain diseases from the planet until the end of time. That’s what we’re working on.