Beyond the Spike: The COVAXX Approach to a COVID-19 Vaccine

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Peter H. Diamandis, PhD, calls himself a “data-driven optimist,” which is a necessary quality for an entrepreneur who relishes tackling grand challenges.

His XPRIZE Foundation has created $10-million incentive competitions focused on the life sciences and other areas, while his venture capital fund, BOLD Capital Partners, has invested $250 million in innovative or “exponential” technologies. His Abundance 360 summits have brought together entrepreneurs, executives, and investors to apply those technologies toward transforming their businesses. His Singularity University focuses on solving global problems through educational programs, partnerships, and a startup accelerator. Diamandis’ companies also specialize in cellular therapeutics (Celularity), personalized machine learning (Futureloop), and longevity health (Fountain Life and Human Longevity).

Another Diamandis company, United Neuroscience, combats animal and human diseases by discovering, developing, and commercializing vaccines and monoclonal antibody treatments. Earlier this year, United Biomedical created a subsidiary called COVAXX focused on tackling COVID-19 through a vaccine as well as through antibody diagnostics deployed in China, Taiwan, and several U.S. states. The company’s serology test is designed to complement RT-PCR testing by helping identify asymptomatic COVID-19 patients and those who were infected and have recovered.

COVAXX’s UB-612 program focuses on developing its Multitope Peptide-based Vaccine against SARS-CoV-2, constructed from a peptide-based platform first deployed by United Biomedical. The vaccine platform has been commercialized successfully in more than 500 million doses annually and 5 billion doses cumulatively in animal health indications for infectious disease.

Designed to activate B-cells and T-cells—both arms of patient humoral and cellular immune responses—UB-612 consists of amino acid sequences of the SARS-CoV-2 Receptor Binding Domain (RBD) formulated with designer Th and CTL epitope peptides derived from the S2 subunit, membrane and nucleoprotein regions of SARS-CoV-2 structural proteins for induction of memory recall, T-cell activation and effector functions against the virus.

COVAXX has launched a Phase I trial of UB-612 in Taiwan, with a U.S. Phase I trial and a readout of data in non-human primates planned this fall. Last week, COVAXX said it will advance UB-612 into a Phase II/III trial in Brazil, through a collaboration with that country’s largest diagnostic medicine company, Diagnósticos da América S/A (Dasa) and vaccine distributor Mafra. They are funding clinical research along with three Brazilian companies: Real estate developer MRV, car/fleet rental business Localiza, and Banco Inter.

Diamandis and COVAXX co-founder and co-CEO Mei Mei Hu recently discussed COVAXX’s approach to fighting COVID-19, and its vaccine development plans with GEN Edge, in a joint interview (lightly edited for length and clarity).

GEN EDGE: How and why was COVAXX established?

DIAMANDIS: There is a parent company called United Biomedical that Mei Mei’s parents built nearly 35 years ago. Mei Mei’s mother [United Biomedical chairwoman ChangYi Wang, PhD] is a very brilliant scientist who developed this concept of synthetic peptides that would be used for vaccines, blood anybody tests, and not only how to construct those, but how to construct them in a way that were safe and were immunogenic, and were really low cost to manufacture. This is a body of work that spans three decades. Out of that work came a series of companies.

The core technology, the core manufacturing was being used to go after different targets. The most prolific and advanced is the work they’ve done with a company that went after foot in mouth disease. Here you have a virulent virus that mutates rapidly. They went after that, in a company that’s now public on the Shanghai Star Market called Shanghai Shen Lian Biomedical.

On a critically important biological product they’re getting this vaccine for their food security, and going from an unknown player to capturing the majority of the marketplace. I think they captured 55% of the market for foot and mouth disease, for vaccinating what’s now over 5 billion pigs. So they’ve manufactured 5 billion vaccines. I think that’s important—it’s the same exact platform.

The important thing here is a platform that is easier to manufacture, low cost to manufacture a vaccine, has been produced at half a billion doses per year or 5 billion doses over time. And is distributed into the rural areas of China. What you should take away from that is, a robust and dependent manufacturing base with a simple distribution network. The other thing is that they manufacture that vaccine for about 70 cents a dose with a very significant margin, so low cost as well.

How and why did United Biomedical shift from animal to human health?

HU: When Lou [Reese], my husband and I, joined over a decade ago, we focused on partnering those animal health assets and moving towards human health. We saw the opportunity to make the broadest impact in human diseases, so we moved Alzheimer’s forward, we just brought it in Parkinson’s—we basically expanded the portfolio, and we’ve conducted four clinical trials off the platform. To our delight, we see a lot of translatability from animals into humans. So the vaccine does everything we want the vaccine to do—it safely generates very high antibodies that are super specific with an excellent profile.

Fast forward to the first quarter of 2020. The world is changing, the landscape is shifting, and it reminded us of the first SARS epidemic where, because of our footprint in Taiwan and China, we were one of the first responders. We actually worked with the NIH to develop an antibody test and vaccine back then.

Starting in December, we were actually one of the first to respond with an antibody test just into the field and ground zero. And we called Peter [Diamandis]. I said, “I think we should respond to COVID-19, we should stand up an effort. What do you think?” That is how, essentially with a phone call, COVAXX was born. We decided to stand up a company that is just dedicated to fight COVID-19. We had no idea how long it would last, or what would be the extent of it. We thought one thing in SARS, and thankfully, that never spread. But COVID-19 seemed like it was different. It has proven to be different.

How has COVAXX gone about developing its vaccine?

HU: We spent a good part of the second quarter basically testing dozens—over 30 constructs—for different properties, and we came down to our lead, which we’re very confident in. It’s based on the same platform. In animals we see really good immunogenicity, very good titers, really good neutralizing ability of these titers. It was designed and culled for B and T cell responses. We wanted to make sure that it hit neutralizing antibodies. We wanted to make sure that it got broad immunogenicity, so we’re not just hitting the Spike (S) protein, but we’re hitting different parts of SARS-CoV-2. We have seen the super heterogeneous response from serology samples, both in the field and our own. We know that people respond very differently. And there are different parts of the virus, not just the S protein, that are responsible for an immune response. So we wanted to make sure we hit all of those.

How does it go beyond just hitting a spike protein, which a lot of the different treatments and vaccines do?

HU: It’s a super rational target. That’s where a lot of the neutralizing antibodies target… It’s the RBD portion of the spike protein. What we also noticed, though, was that a lot of T cell responses, they’re very important epitopes on different parts of the virus.

So, if you look at recovered patient serum, there’s a lot of response to that. So what we did was we selected some important other epitopes on those, because we wanted a balanced response. So we wanted a balanced T-cell response as well. So does it hit it all the same time? In some ways, yes, because the vaccine is introduced to the body at the same time, but they do different things. So we want not just neutralizing antibodies, but we also want T-cell activation, because in our experience we’ve seen neutralizing antibodies are great, but you need both in order to offer full protection.

Could you elaborate on how you go beyond the neutralizing antibodies, what the virus attacks? I noticed that you look at B and T cells?

HU: Yes, it’s B and T cells. So we want to hit T helper cell sites as well as CTL sites. That’s the hallmark of our platform technology, whereas we have these peptide carriers and they help generate immunogenicity. The way they do it is they mimic highly promiscuous T-cell sites.

So they attract all these T cells and then the T helper cells, basically, signal to nearby B cells to produce antibodies. So we do that—it’s a similar thing with our vaccine, whereas we hit both the important antibody sites and the T cell sites. And we do that simultaneously. But what we found is that some of the important T cell sites aren’t just on the S protein. So they’re across the virus. And it’s evidenced in real life data that there are other sites that are important, and that actually induce an immune response that are not just on a spike protein.

You had a platform in place. How much variation from that platform was needed to in order to fight COVID?

HU: The platform consists of manufacturing technology, design technology, screening. We have a different assay group, and then basically just the development engine that drives everything for a new disease indication.

I think of them like our platform is like Legos, or an operating system, and each new disease indication is like an app or a new Lego box. Everything is designed from scratch, but they’re using the same types of building blocks. So, for COVID-19, we were actually fortunate because we had worked on SARS before. So we actually knew a lot about this type of coronavirus, and that’s why we’re able to rapidly put together something in just a couple months.

It’s doing the same technology. And the good news is, now that we’re entering the clinic, the manufacturability, the downstream process in drug development, that’s leveraging the same infrastructure as all the other vaccine programs, which is important, which also gives us confidence in our ability to actually deliver these vaccines.

Is COVAXX still looking at ramping up production to 100 million doses by the first quarter of 2021, and a billion by the end of 2021?

Mei Mei Hu, co-founder and co-CEO, COVAXX

HU: We’re still targeting 100 million doses by the end of the first quarter, and of course we’d like a billion. It depends on the dosing, right? That’s what we’re going to find out. So 500 million to 1 billion doses in 2021.

We manufacture almost all the components internally. So for the fill-and-finishing, these are are going to require collaborations for a variety of reasons: Geography, capacity. But that’s our target and this isn’t theoretical. We’ve manufactured vaccines before, so that’s what we’re aiming for.

What manufacturing will you do on your own? And where are you reaching out? Are there collaborations in place with other partners yet?

HU: We are manufacturing mostly in our facilities in Taiwan right now–really in New York and Taiwan, but the majority is being done in in Taiwan at the moment. We have peptide, vaccine fill-and-finish—so they’re all part of the group there. And we’re in discussions now for certain areas, developing partnerships for the final process.

The company has launched a Phase I/II trial in Taiwan. What is the timing for launching that study in the United States?

HU: Our plan is to actually start a trial with the University of Nebraska Medical Center at the National Quarantine Center later this fall.

DIAMANDIS: I’ve been involved in running a bunch of companies at a time—XPRIZE, Singularity University, my venture fund, Abundance 360. I’ve got typically 5-6 projects going. When Lou and Mei Mei called me at the beginning of March, and I helped them bring in team members and capitalize this and stand it up, I took on a role as a co-founder and vice chairman. This has become my dominant focus, near 90% of my time. And it’s because the opportunity is so massive.

When I look at this, what I see is a vaccine that, number one has high immunogenicity—we do blood antibody testing. So we’re very clear about convalescent plasma levels…We’re seeing immunogenicity that in the lab comes out to 400-fold higher than convalescent plasma.

Can you put that figure in perspective?

DIAMANDIS: So that’s huge. We really do light up the immune system to manufacture antibodies at high rates. The second thing is, are those antibodies functional? Do they work and they neutralize the virus?

When we look at the titer for neutralization and we compare it in preclinical to preclinical head to head against other vaccines out there, we see the Oxford/AstraZeneca vaccine with neutralizing factor of 40. We see Moderna ranging from 500 to 1,000 as comparison. And we’re not at 40, or 500 to 1,000. We’re at greater than 32,000. We’re talking about orders of magnitude higher in terms of neutralizing titer.

If you have high immunogenicity and super high neutralizing titers, this is because of the rational design—we have six epitopes. The multitope design doesn’t just attack COVID-19 and stop it from one angle, one protein. It’s coming at it from multiple angles.

How manufacturable is the vaccine?

DIAMANDIS: The answer is, not only yes but hell yes! Because the platform has been manufactured at scale. The team has made a decision to put everything else on hold, and spin up manufacturing to support getting to 100 million doses in Q1 of 2021 and to a target of a billion doses by the end of 2021. So, it’s manufacturable.

Is it transportable? Can you get it to the end patient? You know, does it require negative 80 degrees nitrogen, like you do in RNA vaccines? No, this is a vaccine that can be transported easily into the rural areas like it does in China, because it’s the same platform. It doesn’t require anything special. It uses the existing distribution channels, so it’s immunogenic, it’s neutralizing, it’s manufacturable.

Is it affordable? The answer again is yes. Now, it’s not going to be as cheap as the animal viruses, because there’s an additional level of quality control and safety. But to remind you, the platform manufactures the foot and mouth disease vaccine at scale for less than $1/dose with significant margins.

So, we have a belief that we can manufacture something that really is extraordinary. It goes into human trials the last week of this month in Taiwan, Phase I/II. The Taiwanese government has been very closely overseeing this and so they’re covering 90% of the cost of those trials as part of their investment.

What, if any, U.S. partners is COVAXX working with?

DIAMANDIS: We have also partnered with the University of Nebraska Medical Center, which specializes in pandemics. It’s really the national jewel for treating pandemics. Within the medical center the Global Center for Health Security, within which is the 20-bed National Quarantine Center, the nation’s only federal quarantine unit. We’re going to be doing our US trials phase I and II with them. We’re lining up a series of other additional trials that I can’t mention right now. We’re pushing as rapidly as we can.

And then there’s one last factor: Is this vaccine safe? I would normally say, “Well, we’ll find out.” And we will. But what we do know is that this vaccine platform—effectively the majority of the structure, the mechanism and all of that, other than the selected short chain amino acids, the peptides—that this vaccine platform has been in four human clinical trials right, in the Alzheimer’s and Parkinson’s efforts that go back to what our sister company has done.

In those trials, it has been absolutely safe with only minimal irritation. It has been a platform that has proven to be very safe in humans. And in those trials as well—which took place in elderly because Alzheimer’s is a disease of the elderly, like to some degree COVID-19 is a disease of the elderly—in those trials, it proved to have immunogenicity in 98% of the elderly in which it was introduced. Again, the science will prove it out, but we have a predominance of evidence that here we have a vaccine that’s immunogenic, super high neutralizing, low cost to manufacture, that is manufacturable, transportable, safe and effective in the elderly. We have super strong evidence to support that. And that’s what gets us all excited, and that’s what’s, from my own personal standpoint, gotten me to put to put everything else aside and prioritize COVAXX.

HU: Then, we’ll be aiming to start the Phase II/III efficacy trial the end of this year, which will require at least four months of safety data. So it’ll run into mid 2021 if not late 2021.

How big of a population are you looking at? Some of the leading COVID-19 vaccine developers companies have been recruiting 10,000 participants, or 30,000, or even 60,000.

HU: We’re actually doing powering estimates right now to make sure that we’re well powered for the efficacy trials. But, you know, depending on the prevalence of these, you know, it does look like it’s a large trial and the thousands of patients will probably do it in multiple sites, not just in the U.S. And one of the reasons is because you want to make sure you get high-quality recruitment, fast recruitment, and that you’re basically chasing where the outbreaks go.

Is COVAXX quantifying its investment in COVID-19? Is it $X million in capital raised, for example, or you can give a figure?

HU: This platform has been developed over the last couple of decades. We’ve invested over about a quarter of a billion dollars into the technology and the underlying infrastructure. So, we have been able to leverage all that for COVID-19.

You said your team went into China very early in the run of the virus. Is there still testing in China right now?

HU: No. What I meant was that when we were developing our antibody tests, we basically sent them early on to ground zero of the outbreak, both in China and Taiwan. We’re doing most of our stuff actually in Taiwan right now.

How does your company’s antibody test come into play here?

HU: As vaccines roll out, antibody tests are going to become increasingly more important. So I think we’re well positioned to offer a complimentary product after the vaccines come on. Now, the question of, do you have antibodies is increasingly important and you want to know if you respond to the vaccine. You want to know if you’ve got antibodies from the vaccine or from natural infection. These are things that our antibody tests can actually differentiate and provide information on.

DIAMANDIS: A lot of these—even natural immunity, we don’t know how long it will remain. And if you get immunized, did you develop a sufficient antibody level? And at six months or a year later, are you still immune? That’s a question which is going to start to be asked in the middle of next year, end of next year. And that’s when the antibody tests will actually be the most useful.

There’s the issue of how long you stay immune once you get this. At least one patient made headlines worldwide as having been infected twice with COVID-19.

DIAMANDIS: Yes, especially when you start to see some mutations in the virus.

Now, what’s with those mutations? How will this vaccine be able to keep up with mutations?

HU: That’s something everyone is concerned about. From a scientific standpoint, it’s still early to tell. We just have to wait and see. That’s actually one of the major advantages with our foot and mouth disease platform: We actually saw a mutation, and we were able to quickly adapt and get out a new vaccine to cover this new mutated strain, and we did that—we basically designed and manufactured in about 60 days, and had it out in the field in the quarter. So this is an opportunity for us to actually shine and create and capture more market share, in the case of animal health.

One of the primary features of our platform is the vast ability to develop and manufacture and adapt to potential mutations down the way. It’s something that we actually are very conscientious about, and feel very well suited to tackle if it comes down the pike.

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