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Welcome to BIOTECH NATION !!! With understandable interviews requiring no background in science, BTN attracts a wide global audience. From everyday people looking for hope in treatments in development, to bioentrepreneurs interested in the experience of their fellow travelers, to venture capitalists looking for possibilities in cutting-edge breakthroughs, to scientists simply interested in the work of others, BioTech Nation is the voice of human endeavor, driving science to new realities for everyone. These interviews are drawn directly from the public radio program, "Tech Nation", which also can be heard in numerous global radio and podcasting venues.
Codagenix of Farmingdale, New York has developed the technology to precisely engineer viruses to do all sorts of things. It's current work to develop a COVID vaccine based not on that versatile newcomer mRNA, but rather as a traditional virus based vaccine is not at all traditional. It would have protected against the omicron variants even before there was an omicron variant. In addition, it's delivered nasally. That's right.
Dr. Moira Gunn:No needle. And its development now in phase 3 is now being supported by the World Health Organization. But there's more. The efforts of codagenyx are wide ranging. New vaccines for RSV, influenza, yellow fever, dengue, and Zika.
Dr. Moira Gunn:Also, viral based therapeutics for cancer and more. What's important is understanding how these viruses can be engineered to have characteristics which not only deliver potency, but also are incapable of mutating into undesirable forms. It's called rational virus design. Doctor Robert Coleman is the cofounder and CEO of Codagenix. He'll explain how this approach changes what's possible in vaccine development and therapeutics in general, And it further has the ability to respond quickly and directly as opposed to the trial and error method used before, doctor Robert Coleman.
Dr. Moira Gunn:Rob, welcome to the program.
Dr. Robert Coleman:Hi, Moira.
Dr. Moira Gunn:Before we get into what we can do today with better technology, I think we pretty much have all had multiple vaccinations at this point right up to and including being vaccinated for COVID. But our vaccination started early, you know, for measles and polio and the list goes on. How would you characterize these vaccines, you know, that we took all throughout our lives, and how are they developed?
Dr. Robert Coleman:Right. That's a that's a great question. So, you know, the those traditional vaccines have been extraordinarily effective at preventing disease. He's been starting when when you were very young. And the best class of those sort of early childhood vaccines that we've all received, our children may have received what are what are called live attenuated or weakened versions of the virus that you're trying to protect against.
Dr. Robert Coleman:So they would take it's actually kind of amazing to believe it was really done through trial and error. Right? So they would take the measles virus, and they would passage it either at cold temperatures or in chicken cells, and it would start to not like humans so much and would convert and it start to mutate away from humans towards chickens. And then we'd actually use that virus to vaccinate ourselves against measles. And so those traditional vaccines have been amazing at preventing disease, because they are live weakened versions of the virus, but they were really made through complete trial and error, random mutation of really unknown results in the virus.
Dr. Moira Gunn:The chickens chickens were involved in their in their development.
Dr. Robert Coleman:They were they were crucial to really one of the biggest advancements of humankind, right, has been for vaccination, and it's really through random changes, which is just kind of amazing to think about.
Dr. Moira Gunn:And once you get one of those vaccines, this is what blows me away, how is the vaccine manufactured? How is it produced?
Dr. Robert Coleman:They don't all use the same exact system, but some still are used. So, for example, a yellow fever vaccine is still manufactured in embryonated chicken eggs where you inject the egg with a little bit of virus. You wait a few weeks. You harvest the vaccine stream from the egg, almost like a egg frappuccino, and that's what we're still using as a vaccine. And it's because we have to use the same system that made those traditional live vaccines.
Dr. Robert Coleman:So that's also sort of ripe for for innovation, but it's amazing to think about that a lot of these live vaccines that we still use sort of have an antiquated approach for production.
Dr. Moira Gunn:Let me ask you. In COVID, the Johnson and Johnson vaccine vaccine was called a viral vector vaccine. Is is that the same kind of thing?
Dr. Robert Coleman:It's not exactly the same. They use a weakened virus, but instead it's more like a Trojan horse. So in that instance, Johnson and Johnson is using a virus called adenovirus as a way to deliver the spike protein to your immune system. So it wasn't like they took SARS CoV 2 and put it in chickens for for weeks on end. So they had an adenovirus expressing a piece of SARS CoV 2 or COVID to get your immune system to make an immune response against spike.
Dr. Robert Coleman:So there's a little subtle difference there between a traditional weak virus or live attenuated that has all of the proteins that you want to go against and the Johnson and Johnson vaccine, which I sort of like to call a Trojan horse that expresses just spike of the that you're trying to protect against.
Dr. Moira Gunn:And don't forget, for all those decades, we did not have the tools to go in and edit a virus, do any of those things. We had to keep trying until we got something that, oh, that works. And then we'll we'll keep that. So we just didn't have the tools that we have today. So so so we could see that the, the viral vaccines are are moving ahead.
Dr. Moira Gunn:At the same time, the Johnson and Johnson vaccine was only 66% effective, while the other 2 COVID vaccines here in the United States, at least, were Moderna and Pfizer BioNTech, which are mRNA vaccines, completely different technology. We're over 90% effective. Does that mean that these viral vaccines will be a thing of the past, and will just be going with the mRNA vaccines?
Dr. Robert Coleman:I I don't think so. Of course, I'm slightly biased, but, I mean, the common similarity between the mRNA and Johnson Johnson vaccine is what I call, They're really just antigen delivery systems. Right? They're bringing an antigen to your immune system in order to engage it and have it make a lot of antibodies against said antigen that they wanna target. So spike in the case of of the COVID vaccines, and the mRNA is just very efficient at doing that.
Dr. Robert Coleman:But I think we see with the current trend in COVID and variants emerging and need to update those vaccines that there's still an avenue if we can somehow figure out to make better live vaccines, that may express not just spike, but lots and lots of proteins of the virus.
Dr. Moira Gunn:Now tell us what codogenic does.
Dr. Robert Coleman:Well, that's, I mean so sort of to perfectly dovetail, thank you, Mora, is that, you know, if you think back to how those traditional live vaccines were made or why were they so great is because they weren't just expressing the spike of the virus. It's actually mimicking the wild type virus. So it's expressing all proteins of the virus, and that's sort of the the next generation codogenics approach is those traditional vaccines may be limited in their genetic stability. So they were randomly mutated to become vaccines. And what codogenics has been able to do is we found a way to recode the DNA of a virus, such that it's genetically stable now.
Dr. Robert Coleman:It will not revert, and it can actually be used as a vaccine that express not taking COVID, for example, not just spike, but all the proteins of SARS CoV 2 to get all the benefits of a traditional live vaccine. Right? Spike immune response, but immune response to all proteins of the virus.
Dr. Moira Gunn:Well, it occurs to me that first of all, you can take the virus you're after and completely decode its DNA.
Dr. Robert Coleman:Yes. So it's actually a completely digital so the way Cotinics really does it is the commonality for all human virus is your body, your nose. Take COVID for example. Or your cells, they wanna come in or the virus wants to come in, make a trillion copies of itself in as little as 8 hours. Now that's a big number, but the virus wants that process to be very, very efficient.
Dr. Robert Coleman:So it's made its genes very, very favorable for translation efficiency or production in the human host cell. And so what we've done is our platform, unlike the other platforms, which I classify as antigen delivery, ours is really a software. So we have now understand how you can encode genes for very, very favorable translation or production in the human body and how you can encode a gene for very, very slow translation in the human body. And so what we can do is we can take the DNA sequence of a virus that's very fast. We can recode it for slow translation.
Dr. Robert Coleman:We can insert that piece of DNA back into their genome. And now we've converted wild type pathogen virus that makes you very sick into live attenuated vaccine. And it's universally applicable to viruses because it's not focused on 1 protein. It's not focused on random mutation. Instead, it's an algorithm that understands how to recode its DNA for for slow translation.
Dr. Moira Gunn:So simply by slowing down how fast it replicates, you're weakening it, number 1. Yeah. So when you say, okay. In in one sense, if they could have done that a 100 years ago, what great shape they would have been. How do we slow down the virus?
Dr. Moira Gunn:And then right now, we're saying, well, what do we have to hit? You know, we're trying to get very excited about it. And you're saying, wait a minute. There's a lot of stuff we may not know. If we can slow down the whole thing, then the aspects that we don't yet understand won't matter because they'll be engaged in the human host.
Dr. Moira Gunn:Right. Wow. I gotta write on that. I like that. Sometimes they say, well, it's not like that at all.
Dr. Moira Gunn:So I'm really thrilled. I'm really thrilled. Now I just wanna ask a slightly different question here. I know that the the Pfizer BioNTech and the Moderna, COVID vaccines had to be in these special freezers from the or or refrigerators, deep deep freeze, deep deep cold from the point they were refrigerated to the point of delivery. Is that also true with these viral vaccines?
Dr. Robert Coleman:No. That's actually so, yeah, you can see that in order to keep the RNA stable, they have to use minus 80 degrees Celsius freezers. They have to ensure that the repository has those freezers. You see that they wanna make the expand this ultra cold chain to sort of increase mRNA uptake around the globe. One of the best aspects of weak virus vaccines is that they usually only require a standard freezer or refrigerator.
Dr. Robert Coleman:Sometimes they can even be lyophilized or turned into powder that can be reconstituted. And as you can see, and sort of one of the best examples for this is smallpox. Right? In order to eradicate smallpox, they had a very, you know, standard refrigeration or lyophilization for the vaccine. They didn't need to make freezer farms around the world, in order to eradicate smallpox.
Dr. Robert Coleman:And so that's sort of one of the traditional benefits and global access for live vaccines is their ability to be, you know, stored in sort of standard conditions.
Dr. Moira Gunn:Now you've just finished phase 2 going into phase 3. I think you've started phase 3. The last phase of clinical trial before approval, on your own COVID vaccine. And I understand that this work at at Cotagenyx is supported by the WHO. Now there are easily a dozen COVID vaccines around the world.
Dr. Moira Gunn:Why are they supporting your particular endeavor?
Dr. Robert Coleman:Well, that's a that's a good question. It sort of, you know, speaks to your last point, and I think the actual number on the WHO chart is a 194 next generation vaccine candidates. And why did they select codogenics was well, firstly, they I think the WHO recognizes the benefit of live vaccines, right, and what they're capable of doing. But more importantly, what we've been able to show with our COVID vaccine for firstly, it's intranasal. So it can has a potential to block transmission, induce mucosal immunity.
Dr. Robert Coleman:But we showed in our phase one was demonstration of efficacy or potential for efficacy, excuse me, potential for a global distribution. So our we're partnered with Serum Institute India that has massive ability to for commercial scale of the product. But more importantly, some of the data from our phase one was that we showed not only do we show a 100% antibody or seroresponse rate in the participants, we showed muk the induction of mucosal immunity that could slow down replication of a SARS CoV 2 virus. And to me, the coolest piece of data that sort of circle back circles back to your original question, Moira, is when we looked at the t cells or the cellular immune system response to our vaccine, we saw that all of the participants or on average, the participants in the vaccinated group made a fivefold increase in their anti omicron cellular immune response.
Dr. Moira Gunn:So it included omicron.
Dr. Robert Coleman:Well, the cool well, I didn't actually get to the coolest part yet. The coolest part is that this trial was done in early 2021. So this is when the individuals were being vaccinated. When we measured their t cell response was towards the end of 21, but they made this omicron response before the omicron strain was actually prevalent. And they made the response to all the other proteins of SARS CoV 2, not just spike.
Dr. Robert Coleman:And and so this is why sometimes live vaccines are called the sort of gold standard where they may only require a few doses. They pro provide very, very long term immunity. It's because they cover the span of the proteins in the virus. And to me, that's the coolest thing. Right?
Dr. Robert Coleman:Our vaccine recipients made an anti omicron cellular immune response before the virus was even on the scene.
Dr. Moira Gunn:While that is exciting, I have to tell you there are some people listening. A few of my friends among them who held out for the Johnson and Johnson virus because it was only one shot. Big strapping guys who were afraid. They said, just give me one shot. So when they hear, this is intranasal, you're just gonna spray this up my nose?
Dr. Moira Gunn:They'll be the first in line. You know? It's like so you don't have to have a shot. And we don't know how big the, immunity will be. But we know that you're not just focused on the one spike protein.
Dr. Moira Gunn:You're saying, well, let's just take the whole cell. Let's just take the whole virus and, and use that. That's very exciting.
Dr. Robert Coleman:Especially because the proteins that so why are variants emerging is because the spike protein is the virus that the is the protein of the virus that mutates the most. Right? Trying to avoid antibodies. All the other proteins that sort of run that, the machinery of the virus, they mutate very, very slowly, and that's actually what you make your cellular immune response against. And so if you can have vaccines that induce cellular immunity to the to the proteins that don't mutate as rapidly, you can get this very, very, very broad immune response.
Dr. Robert Coleman:And we're hoping to show that in the the WHO trial. It's a placebo controlled trial. It's occurring Africa, potentially South America, potentially Southeast Asia. And right now we're you know, it has a daunting task in the sense that it's a placebo controlled trial looking for efficacy against Omicron, and I think we have real potential to do that based on what we saw in in our early clinical development.
Dr. Moira Gunn:So now let's, talk about vaccines and cancer. Cancer is not an infectious disease. I mean, we don't usually think of cancer and vaccines. What are you doing in that space?
Dr. Robert Coleman:Yeah. Well, I would you know, I think sometimes people see the Cotigenics Oncology vertical that we're growing, and they use the word cancer vaccine. It's not actually a cancer vaccine, and so we're designing viruses that we can inject into tumors that help recruit the immune system to the tumor and help clear the tumor. So it's really a next generation immune oncology therapy. It's not a cancer vaccine.
Dr. Robert Coleman:Sorry to correct you. But, Okay.
Dr. Moira Gunn:No. It's alright.
Dr. Robert Coleman:What we found though is that what we found is that the algorithm, once we started designing these viruses for to be safe in immunogenic vaccines, we also learned that the algorithm that understands the human genome and how to encode the genes can also be used when appropriately implemented to design viruses that are very, very potent treatments for solid tumors. And I think the way to sort of separate what codogenics is doing from other, you know, the fields called oncolytic viruses or viruses to treat cancer is that we can take the inverse the opposite approach. So most people have one virus and they're trying to see which cancers they work in. And so we can leverage codagenyx algorithm to instead take the opposite approach. Pick a cancer, screen viruses, design a cancer against, excuse me, a virus against said cancer.
Dr. Robert Coleman:Now we've had a custom immune oncology agent for whatever cancer indication you're pursuing. And and sort of really codogenics is in the virus design business. We leverage the human genome. We leverage synthetic biology, the the ability to design DNA however we want. And now we can design viruses either turning them into prophylactic vaccines to protect against infectious diseases like COVID or RSV or dengue, or we can use the same algorithm to design a virus that's safe and also really likes to infect, kill, and and recruit the immune system to a tumor.
Dr. Moira Gunn:Now let me get this straight. In all of these cases, you are building, engineering, designing viruses and it's when you finally get to something you like, you take that virus and you replicate the virus and that virus is exactly what you're injecting. In the case of of the the COVID vaccine, and its trial now, you're injecting that intranasally right into my nose.
Dr. Robert Coleman:Yes.
Dr. Moira Gunn:Just giving me the virus.
Dr. Robert Coleman:But we've been I mean, it wasn't right off the shelf. Right? 1st, we had to show to the regulators that it was safe and, you know, safe in preclinical. It was safe in phase 1. And and also to sort of circle back to the initial problem that CotoGenics can solve is that, keep in mind, you know, those traditional live vaccines usually rely or traditional live week vaccines usually rely on a limited number of genetic changes.
Dr. Robert Coleman:What CotoGenics does is we insert 100, sometimes thousands of genetic changes that make the virus unable to revert. And so we can actually pull the vaccine strain out of the noses from our COVID trial. Now there was a little bit in there. It it wasn't very high level. Every the, the the safety profile was great.
Dr. Robert Coleman:But more importantly, when we pulled the vaccine out, there were no mutations in the in the designed region showing we really proving the concept of supreme genetics, genetic stability using our design approach.
Dr. Moira Gunn:So once you spray it in my nose, I got it in my nose forever?
Dr. Robert Coleman:No. No. No. No. No.
Dr. Robert Coleman:No. It goes so the wild type would be there for 8, 9 days, you know, orders of magnitude shedding capable of spread, right, to other individuals. Ours was there for a few days below, for the most part, the threshold for spread, and it disappeared within a few days too. But when we would wait for the tail end to see if we could find it, we would sequence, you know, with with, we would we would sequence the virus, and we could show there were no mutations, which I think the regulators really responded to as well.
Dr. Moira Gunn:How many people work at Cotogenics?
Dr. Robert Coleman:Right now, we're at 28 individuals.
Dr. Moira Gunn:28 people.
Dr. Robert Coleman:And growing and growing.
Dr. Moira Gunn:Well, you're not gonna get to 28,000 in the next week. You got 28 people. You've partnered with people. You're you've partnered with Serum Institute India. You've got and that's just this is just on the COVID.
Dr. Moira Gunn:You've got, WHO supporting you. You've got all of the other vaccines that you're working on. I'm very interested. How did codagenyx get started? Who were who who was involved?
Dr. Moira Gunn:How did this all come to be?
Dr. Robert Coleman:Well, that's that's a great question too. So we came from so I was actually the graduate student pipetting, you know, some of the first work that became the core of CotoGenics. My other cofounder, Stefan Mueller, our chief scientific officer, to me, one of the most pivotal, you know, players in early synthetic biology. And then the 3rd founder, Eckhard Wimmer, was the first to actually synthesize a virus completely from small oligonucleotides, National Academy of Science members. So the 3 of us nucleated the company.
Dr. Robert Coleman:We raised our initial money from NIH and then investors got interested. So the company started at just 2 individuals and now we're up up to 28 and we emerge from, you know, probably one of the earliest synthetic biology labs there was at at Eker's lab at Stony Brook University.
Dr. Moira Gunn:Well, let me let me, translate a little of this. Sure. Synthetic biology is when you literally, you don't just deal with a small part of a virus or a small part of DNA, in any kind of cell. It means that you program the whole thing. You take the whole thing and you program the whole thing and it works and it is alive.
Dr. Moira Gunn:So that's part of it. But I have never heard before that anyone saying that they they they these people got together and nucleated the company. What you did is you gave it the whole DNA, and that's how the company got started in a in a synthetic biology sense.
Dr. Robert Coleman:Sure. Exactly. I mean, the the thing is if the what you think about what Ecker did in our lab did with that viral synthesis was, you know, if you could take small pieces of DNA that you essentially ordered through your computer and you could stitch that together to make a virus, you're no longer bound by this to the natural sequence of the virus to make designs, to learn, to mutate it. Right? Those are traditional weak vaccines.
Dr. Robert Coleman:Really, we're just variations of the natural sequence. Right? They were just mutated in a chicken, as we said, our cold temperatures. If you can order the virus and design it on your computer, you can now mutate it extensively, and that's really what codogenics has done. We understand how to encode human genes to slow them down, and now we can leverage our experience with stitching this design DNA into a virus.
Dr. Robert Coleman:And now we've developed a platform, but again, it's not an antigen delivery, right? We're not using adenovirus to carry spike or a virus like particle. You have an algorithm where you input the wild type sequence. It gets redesigned into a slow new sequence that has hundreds of mutations that when we put back it in into the virus, it converts it from wild type that makes you sick into one that can be an effective vaccine presenting all proteins to the the immune system.
Dr. Moira Gunn:Well, I I now understand why your motto is, engineering viruses to transform global health. But I'd like to I'd like to suggest another one. Just, it's really simple. Chicken free. I think I think that's where you should go with it.
Dr. Moira Gunn:I can see the logo. I can see it. I want one of the t shirts when you do your chicken free chicken free T shirt campaign.
Dr. Robert Coleman:I'll make some
Dr. Moira Gunn:okay. Rob, thank you so much. I hope you'll come back and talk to us again.
Dr. Robert Coleman:I would love to give you an update sometime in the New Year on on as the data's rolling in across the programs more.
Dr. Moira Gunn:Doctor Robert Coleman is the cofounder and CEO of Codagenix in Farmingdale, New York. Since this recording, the rise of RSV in infants and young children and the impact of increased hospitalizations in pediatric wards has been widely reported in the mainstream media. There are no currently approved vaccines. Codagenix nasally delivered RSV vaccine has been fast tracked by the FDA. The initial study in healthy children aged 6 months to 5 years is expected to begin in early 2023 after this year's RSV season with a confirming study in the 2023, 2024 RSV season.
Dr. Moira Gunn:More information is available at codagenix.com. That's codacoda, genix, genix.com. For Biotech Nation, I'm Moira Gunn.