Radio Cade

How to Create a COVID-19 Vaccine

June 23, 2020 Alan Joslyn
Radio Cade
How to Create a COVID-19 Vaccine
Chapters
Radio Cade
How to Create a COVID-19 Vaccine
Jun 23, 2020
Alan Joslyn

All sorts of organizations, big and small, are attempting to create a vaccine for COVID-19.  While big pharma has access to seemingly endless resources, even small organizations are obtaining funding for their vaccine ideas. Alan Joslyn Ph.D. President and CEO of Oragenics Inc, has spent 20 years in Big Pharma and has been the CEO and Director of several privately held companies. Join us as we discuss COVID-19 vaccine challenges and explore Oragenics journey from idea generation to COVID-19 vaccine testing. 

Show Notes Transcript

All sorts of organizations, big and small, are attempting to create a vaccine for COVID-19.  While big pharma has access to seemingly endless resources, even small organizations are obtaining funding for their vaccine ideas. Alan Joslyn Ph.D. President and CEO of Oragenics Inc, has spent 20 years in Big Pharma and has been the CEO and Director of several privately held companies. Join us as we discuss COVID-19 vaccine challenges and explore Oragenics journey from idea generation to COVID-19 vaccine testing. 

Intro:

Inventors and their inventions. Welcome to Radio Cade the podcast from the Cade Museum for Creativity and Invention in Gainesville, Florida. The museum is named after James Robert Cade , who invented Gatorade in 1965. My name is Richard Miles. We'll introduce you to inventors and the things that motivate them, we'll learn about their personal stories, how their inventions work and how their ideas get from the laboratory to the marketplace.

James Di Virgilio:

Welcome to another edition of Radio Cade . I'm your host, James Di Virgilio. Today. We revisit vaccinations, but last time while we took a broad lens look at what is a vaccine and how does it work. This time our guest Alan Joslyn , who has a PhD in biomedical pharmacology is going to walk us through what it's actually like to be working on a vaccination, what it takes to get it to market the hurdles that you face. And really just how much goes into finding a successful vaccine. Alan Joslyn is the president and CEO of Oragenics Incorporated. He spent 20 years in Big Pharma and has been the CEO and director of several privately held companies during his career. Alan , welcome to the program.

Alan Joslyn:

Hi James, thank you. It's a pleasure to be here.

James Di Virgilio:

So last I spoke about vaccines, we had a fascinating conversation with Dr. Peter Corey of Ology, and I know today is going to be yet another one of those. Tell us a little bit about Oragenics and i t's rather recent shift a nd what i ts core portfolio is.

Alan Joslyn:

Well, Oragenics is actually originally a spin out of the University of Florida back in the mid 1990s, working primarily in the areas of oral health development of probiotics, and also developing a brand new class of antibiotics called Lanta Biotics that we've been working on for upwards of 20 years. And recently we had the opportunity presented to us to take on a vaccine candidate that was originated actually from the national Institute of Health and a private company in the Gainesville area. Noachis Terra was fortunate enough to license that product in and we moved forward and acquired Noachis Terra just a month ago to jumpstart development of this COVID-19 vaccine.

James Di Virgilio:

Now, why get into the game seemingly this late? Right? I read today that Moderna is going to reach its final stage of testing. I learned from Dr. Peter Corey that really only 16% of vaccinations even make it to the end of their trials with any sort of success. So of course one could argue that that's probably what you're doing, but when you were looking at this, why take on this challenge now, are you late to the game or is this the right time?

Alan Joslyn:

Well, it's really important to understand that, especially in vaccine development, it's not necessarily the fastest to the endpoint . It's those vaccines that produce the greatest immunogenic response coupled with safety. This particular vaccine that we've in licensed is much more of a traditional approach to vaccine development in that it takes and creates an antigen to that spike protein that we read about and see on the nightly news. And that spike protein is what's key to how we go about developing this more traditional approach to a vaccine, create an antigen, supplement it with an edge event and deliver it the way we normally develop vaccine candidates. It takes longer to do that. The technologies, for example, that you read about with Moderna , those are very, very new ways to try and create vaccines with both on proven safety and efficacy as a measure of neutralizing antibodies. And so we don't really know yet what's going to work and not work in the longer term. And so having a variety of different approaches to vaccine development is where we need to go as a society. Having said that there are so many patients on this planet that are going to require this treatment, that more than one vaccine is going to be required to cover everybody. And I don't really think it's too late at this point to try and get into the game. It's more important to make sure that there are options in the event that is Peter Corey inferred, that very, very many vaccines never make it farther than early testing. And hopefully ours is one that's able to survive that gamut.

James Di Virgilio:

You bring up a really important point, whether you are a creative or an artist or an entrepreneur or an innovator, the reality as a human is you have to find the right question to ask, and then you have to try a lot of different solutions to figure out what is the best one that is essentially what you just described for us. What makes a successful vaccine? We're all reading all the time about vaccination is really important against the battle with COVID, but what would actually be success? Is it 50% of people that get treated response 70%? Is there some number out there as you're thinking about Oragenics developing this vaccination, that would say if we got to this level, we could feel good about this really impacting the world.

Alan Joslyn:

Well, that's a fantastic question because there's no hard and fast number that we put on what some measure of success. So, for example, one measure of success is being able to inoculate vast, vast portions of a population in an area and looking at what is the incidence of a particular infection in that area. And have you damped it down enough to be able to manage those few patients that may actually develop the condition. So think of chickenpox is an example. We inoculate everybody. Then you hope that there's only a few cases each year, smallpox, even the same way. We've all gotten inoculated against smallpox . It's effectively eradicated. You may look at this particular situation a little bit different for COVID-19. If you're willing to take the notion that if I get vaccinated and I might only get mildly sick, that might be considered a success as opposed to never having any symptoms at all. So as we, as a society kind of move through this vaccine situation, there will be different measures of success based on what we, as a society determine will be success. I might be willing to go ahead and get a little bit sick, like get the flu, but I don't want to be hospitalized. So you can see where based on what society is after with these vaccines, we'll have different measures of clinical success.

James Di Virgilio:

All right, so the free market is, in my opinion, the most effective tool at solving problems. Of course, nowadays, that topic is oddly controversial. We'll leave that for another time, but I'm imagining hundreds, if not thousands of labs across the world, working on solving this problem in order to solve this problem, you need resources, those resources start off by needing funding, needing money. So Oragenics looks at this and says, Hey, I think that we can open our lab up to this. We're going to use our resources to solve this problem. How do you go about raising money for something like this when there's so much competition?

Alan Joslyn:

Well, in this particular instance, when we acquired Noachis Terra, we also acquired their grant applications for non-diluted funding. And what I mean by that is there are government agencies and nonprofits like the Gates Foundation that are making money available to companies, whether they be Big Pharma or small, like, Oragenics to be able to advance good ideas, such as some of these vaccines. And so part of that was applying for grants through part of the Department of Defense called Barta . And in our case, we've asked for a sizeable grant to help with development through that agency. And of course there's the national Institute of health where this original technology came from. They also have grant programs to help support the development of these programs. We're trying to work also through the state of Florida and also international agencies, including the Gates Foundation and the World Health Organization. But having said that, it also as a public company, I have access to, for example, hedge funds and other life science, investment funds, family offices that are willing to take that financial risk with the idea that my stock price would go up after that investment meets milestones. And for example, over the last of days, I've been at a virtual investor conference, doing exactly that, presenting to potential investment funds that would look in a financing to provide millions of dollars to, Oragenics to advance not only the antibiotics, but also the vaccine with the idea that as these products mature, my stock price would go up and they would be able to realize a profit.

James Di Virgilio:

All right, so what's the pitch? What is leading these investors to believe that investing with you is better than investing their dollars somewhere else? What's the difference? What is essentially influencing them to want to invest with Oragenics?

Alan Joslyn:

Well, in the case of the COVID-19 vaccine, I think that speed is critical and the ability to raise non-dilutive funding because non-dilutive funding what it ends up doing for me is essentially reimbursing me for the money that I'm spending today, that the investor's willing to give me today. So in this particular case, investors like the story of COVID-19, they liked the fact that the National Institute of Health was essentially the inventor. So there's this built in credibility that, wow, this is coming out of the NIH. And so therefore it must be pretty good if this company bought that license and the government is standing behind it. So you have this aura around the science that helps to sell the story. And as long as I'm very clear in not only the timeline that it's going to take me to meet certain milestones, I can accurately project my budget, that investors willing to go along for that ride.

James Di Virgilio:

So why the bad rap for Big Pharma, and now you're on, let's call it a smaller pharma, right? Or biotech. You spent a lot of your career in Big Pharma. Why does the public give Big Pharma such a bad rap? If they're trying to solve some of the most important health problems, the world faces.

Alan Joslyn:

If you remembered before the COVID-19 pandemic, pharma was getting, Big Pharma was getting a bad rep primarily because of how they've handled situations like the opioid crisis and how Big Pharma has managed some of the other side effects and the top part powder with J and J. And they seem to get dragged into these situations. They have clearly the financial and people resources in times like COVID-19 to bring together very, very focused, large teams of people that are very, very competent to doing their job and manage through a situation like this. When you look at government task forces, for example, active, you see the vast majority of the Big Pharma companies sit on that task force because not only do they have expertise, scientifically they have the pockets and the manpower to be able to pull a particular situation through like development of drugs, like REMS Denavir, or a new vaccine, whereas small biotech, we can make decisions very quickly, but we don't have the deep pockets or necessarily the manpower to be able to do a Big Pharma's capable of doing when they get aligned.

James Di Virgilio:

So a criticism of what's even happening now of those that don't favor market based solutions. They would say, Hey, Alan , this is nice. This is great. But essentially these companies are really only investing in the COVID-19 vaccine because it's going to make them really rich. It's going to make them excessively rich. Is there not a better way to do this? What if we just had the government searching for solutions? And if they found a vaccine, they wouldn't get excessively rich. What do you say to a challenge like that?

Alan Joslyn:

Well, I think in this particular case, it's important that everybody realize that all of our businesses have been negatively impacted by this COVID-19 pandemic. And that's inclusive of big pharma. So I'll give you examples. If their sales reps can't effectively go in and detail their products and hospitals, their supply chains have been disrupted. Their research with universities has to some degree, been what's more difficult because of the lack of ability to get into labs, et cetera. So we need to understand that they, as a group have also been negatively impacted by this pandemic and the sooner that we're able to develop solutions and come out of this pandemic as a general society, we're all going to be better off. They happen to have both the scientific and resource capabilities, both human and financial to drive improvements that the rest of us can't and the sooner that happens, the sooner our lives become much more normal than they are right now.

James Di Virgilio:

Yeah . And I think when you're looking at problem solving, you always have to look at what is the most efficient way to solve a problem. I think if you look throughout history, if you look at a nationalized solution where you have a government committee, just government actors attempting to solve problems, it certainly is slower, oftentimes much slower than something that free market could do. And there there's always a trade off between what's profit and accepted profit, but what's risk and reward. And that's a topic for another day, but you mentioned disruption and you mentioned the changing situation in the world. I know that right now you're working from your home, which is not anywhere near where your company is based in Florida. And you've been doing this for a couple of months. How difficult has it been to run a company of your scope and scale during this kind of time remotely?

Alan Joslyn:

That's a great question. I must say that there's eight people in the company and we've just taken on a couple of more with the acquisition of Noachis Terra, our corporate offices are in Tampa, Florida. We have laboratories actually just outside of Gainesville in the Sid Martin Biotech Center in Alachua. And then we have other office space in Gainesville . So for the few number of people we have in the company, we're actually pretty far spread out. As I mentioned earlier on in our conversation, I actually live just outside of Philadelphia. The head of my clinical research operations group lives in Pittsburgh. And what we do is we effectively use laptops and cell phones and scheduled meetings to really run the company. And of course, in my role, as a CEO, I'm traveling to all of those places on a pretty regular basis. Obviously over the last three months, I really haven't been able to do much traveling or any traveling that didn't involve just driving a car. And as a result, you rely much more on technology, but there is clearly a place for face to face interaction. And I expect that to start happening actually next week. But in the meantime we do the best we can working remotely. And we haven't missed very many beats because in a sense, we've been a virtual company for literally the last four years that I've been the CEO and continue to work that way, even through this pandemic,

James Di Virgilio:

Here at the Cade we 1like to talk a lot about how inventors problem solvers , engineers, creatives, all the different terms we can use to apply to people that are out there trying to make the world a better place. They view problems and disruptions in life, not as hurdles to be negatively concerned with or affected by, but as opportunities to learn, grow, do something different. Essentially flexibility becomes the term, right? If we're saying, Hey, I'm going to solve this problem, Alan, you and I are going to get together and we're going to solve this problem. We know we're going to face hurdles, no matter what those hurdles are, we're going to find solutions. You've spent so much time leading companies. Do you feel like that is part of your mindset? Is that, Hey, I know life has hurdles and I'm going to find ways to solve and improve the problems in the world around me.

Alan Joslyn:

I would absolutely agree with that. And I think that our acquisition of Noachis Terra speaks to that straight away. We were first introduced to that company and the opportunity on April 15th and by May 1st, we had essentially closed the transaction to acquire that company. I think it's really important when you're in a role like I'm in is to make sure that you're aware of the right opportunities and the right strategic fit and not be afraid to go after something that makes sense for the company. It makes financial sense is a strategic fit. And you have the support of both in my case, as a public company, my board of directors and my key investors, and in this particular case, or sitting in the middle of a pandemic for COVID-19 and when someone puts a very scientifically credible opportunity in front of me for a vaccine, even though I've never developed a vaccine ever before, it is worth the risk to go down that path, because not only is there the opportunity for the company, it's clearly improving mankind, should I be successful here.

James Di Virgilio:

Yeah. And you're looking at things on a probabilistic curve, right? I'm an investor. I was a professional trade and everything I do is based upon what's the probability of this working. And if I can do this enough times, how often will this work and then you make decisions. And I think increasingly in our society, we're struggling to understand the role of science, the role of problem solving. It is not something that, you know, ahead of time, it is not something that you can predict. In fact, you really have to dive into it and try things and understand that failure is what gives you information to eventually build out a probability curve that says, Hey, if I do this action this many times, the result will likely be good. And that's kind of what you're describing now with your company, Hey, we haven't done this before we have the resources. I think the odds of this and the reward that exist and what it does for society, make it worth it. And I also know that failure is high. There's a real chance that this doesn't work, but that doesn't mean I shouldn't embark on this journey right?

Alan Joslyn:

That's absolutely true. As a matter of fact, we have a program attempting to try and prevent oral mucositis. The name of that drug was AGO13, and we just completed a clinical trial. And the results from that clinical trial were we were not able to separate on our primary end point from placebo. And as a result, we spent probably the last six weeks calling that data set to try and understand what happened better. We actually think now that we understand how that drug works better after all of these analyses. And in hindsight, we would probably do some things different within our clinical trial design for the next clinical trial. And this is all part of the learning with science. I mean, you can't be afraid to fail cause it's going to happen and hopefully your investors are forgiving and that they understand that. And in this particular case, it may not be the best time for us to advance AGO13, given everything else that we have going on. But that clinical trial taught us a lot about how treatments in oral mucositis, in patients receiving cancer chemotherapy , how that particular condition evolves and what are some of the best ways to try and manage that condition in cancer patients. But you're right. You have to be willing to accept the challenge. And in the event that you fail, it's kind of part of our landscape and biotech to have this happen from time to time.

James Di Virgilio:

Yeah, absolutely. If you ask the right questions and you go about trying to answer those questions in the right way, failure just means that your proposed solution didn't work, but you learned a great deal about what may work next. So let's imagine that your vaccine works. We get down the road, this works, this is great. How do you get this to the people? I'm reading a lot about how difficult it's going to be with regards to supply and demand because there's going to be virtually unlimited demand and there's not enough glass files and there's not enough things you need to distribute a vaccine. How would you overcome a hurdle like that?

Alan Joslyn:

Well, it's really important to realize that in the event that this vaccine works the likelihood, and this is again where Big Pharma comes in, the likelihood is, is that I would need to partner this and share in the wealth with companies that have the capability for production and distribution. It will be virtually impossible for a company, the size of Oragenics to pull that off without either extensive government resources through the Barden Network or some sort of a licensing deal with a Big Pharma company that has the capacity for a vaccine that works. Cause remember, as Peter Corey had mentioned, the likelihood is high, that many of these vaccines will not produce the clinical profile that allows them to move forward. And we also know that many of these vaccines are partnered right now with Big Pharma. Our vaccine is not yet partnered, but that doesn't mean that with success down the road, that it would become partnered. And we have to look at the benefits of Big Pharma and that notion of manufacturing and distribution is clearly one of the big benefits for Big Pharma that also holds true for our Lanta Biotics, right? I'm developing a compound to treat Clostridium difficile infection, and it would not be unreasonable for me to reach out to bigger companies that have the capacity to be able to manufacture and distribute those types of products down the road.

James Di Virgilio:

There's a famous illustration that Milton Friedman gives with the humble pencil. And nowadays no one really even uses a pencil much to write on anything, right? But during it, he talks about how the pencil itself has all these components and it comes from all over the world. And the reason for this is not because of complexity, it's actually simplicity. You can make the pencil much cheaper and much more efficiently made. If you're able to leverage everyone else's resources, essentially specialization. I think what you just laid out there as a nice example of that, Hey Oragenics is going to fulfill this role. And then we're going to have to use others that fulfill their roles and together we create a synergistic solution, which betters the world. Now here's an interesting thing. One third, one third Alan of American people say that if a vaccine existed today for COVID, they wouldn't take it. How do you overcome the skepticism or the growing skepticism? The public has towards vaccinations in general?

Alan Joslyn:

I didn't know that that that survey had been done. And in some respects, I'm not quite sure how to respond to that because I can tell you that if a vaccine allowed me to re-enter society from the standpoint of feeling better, to go into a restaurant and be able to sit down for a meal, which up here in Pennsylvania, we still can't do. And I can return to flying on an airplane and not having to wear a mask while I'm sitting on that airplane because I've had a vaccine and these are normal components of my life. I'd be willing to take that vaccine. What's incumbent as we move through, this is that companies not take shortcuts. And that companies make sure that they're completely transparent with their reporting out of the safety and the magnitude of the efficacy that can be reached with some of these vaccines. We've all had our polio vaccines and our smallpox vaccines. And the vast majority of us have had chicken pox vaccines. And so we've not really had to deal with some of the bad viruses that could really cripple our lives. And Coronavirus may fall into that category. We don't know it's not been around for very long, but just a few months, if this keeps recurring in society, hopefully attitudes change. And that vaccine becomes one of those ways to quickly reintroduce some degree of normalcy in our lives.

James Di Virgilio:

Yeah. When dr. Peter Corey was on, he spoke at length about the risk of vaccines, and he's obviously very well informed on the topic, especially having worked for the Gates Foundation. And it's interesting to note that he had said that essentially, there are very, very few examples of vaccines, even trialed ones that make it through and are early onstage . That's kind of the fear, right? Well, Hey, if we release a COVID vaccine, it's not going to be tested for five to seven years. There are very few that wind up being worse than what the vaccine is trying to treat itself yet. It seems like the public thinks that the average vaccine is probably worse than getting the flu or getting COVID or getting whatever it is. It's an interesting scenario that raises a big question about why in general is society not trusting information that maybe we do know to be true, right? This stuff's not predictive. We can look at the data sets. We know these things, aren't your you've spent 20 years. You have a PhD in biological pharmacology, you are looking at the data, you know, what is good and bad? Why is there this disconnect in your opinion, why are people so unwilling to believe some of these things that could be good for us are so bad for us?

Alan Joslyn:

I think that part of it is the level of information flow and transparency from the vaccine manufacturers and distributors to the public. And one thing that we don't do particularly well is inform society in general, is on an ongoing basis. And this goes across the board as to what is really happening with respect to safety. What are the types of side effects that we see with a particular and how frequently do they occur? And is there a special group of patients are subjects that are more prone to a side effect than another group. And I think that if we did a better job of laying that out to a population like the U.S. population, they could make a better informed decision. You're absolutely right. I look at data all day every day, and I have an educated view on things such as the side effect profile of a vaccine, but the general public doesn't have access to that level of information to make a more informed decision. And that's incumbent on us to do a better job of communicating what we are seeing and what are those limitations, because we may find that you could have six different technologies for COVID-19 vaccines that are available in the marketplace, and they may actually be better each one of those six for different populations of patients and having individuals go ahead and be better informed as to which particular vaccine fits their profile. Maybe it's pediatrics for one elderly for another by race for a third. So we have to do a better job in the industry of making sure that we're providing the proper information to the folks who have to make a decision, whether to go ahead and be inoculated. And I don't believe that we've done that particularly well.

James Di Virgilio:

Yeah. One of the most important lessons I learned in my own life was to stop reading articles was to stop what I call end of the chain knowledge learning, but go up to the top, start with academic studies that have been done. And don't just read one that supports your own thesis, read all the ones that exist and get an idea. What do we know or not know about this? And then from there read the people like yourself that have maybe written books and they spent their lives doing the things and read the ones that disagree with each other, because you can have the same set of data, but you can interpret it differently. And if you really want to learn something, you gotta start up top, not down at the bottom, again, no disrespect to any journalists , but you're just getting a little piece of the puzzle and you can form some opinions that are really not so great. So what I want to ask you about here to conclude today's episode is this, Looking back and let's imagine yourself now you're working on your PhD, right? And you're working towards your future. What are some words of wisdom that you would give yourself? If you could go back in time and say, Alan , here's what I want you to know about what your future is going to look like. Here are some things to focus on and here are some things not really to get stressed about.

Alan Joslyn:

One, I think that probably throughout my career, one thing that that I've learned is that failure is going to happen and it will happen from time to time, especially in science. And the failure is educational as well as the successes. And I think our recent clinical trial is the most recent example of that within Oragenics. And as you had mentioned earlier, the notion that failure can create opportunity is exactly that. And if I was young and doing this again, I'd get less stressed out about the failures because you just kind of take that education and apply it. And in our case, being able to quickly pivot and become a new kind of company was success that emanated from failure. And this, especially in science, is going to happen with a certain degree of regularity and has for me over the last 35 years. And there's no getting around it. So probably stressing less about the failures. That would probably be my one key take away message that I've learned having done this for as long as I have.

James Di Virgilio:

That's a great takeaway. He is Alan Joslyn, the president and CEO of Oragenics. Also a very experienced gentlemen with regards to all things pharma, Alan , thanks so much for joining us today. Really a great conversation.

Alan Joslyn:

I appreciate the opportunity and look forward to it in the future.

James Di Virgilio:

For Radio Cade I'm James de Virgilio.

Outro:

Radio Cade is produced by the Cade Museum for Creativity and Invention located in Gainesville, Florida. This podcast episodes host was James Di Virgilio and Ellie Thom coordinates, inventor interviews, podcasts are recorded at Hardwood Soundstage, and edited and mixed by Bob McPeak . The Radio Cade theme song is produced and performed by Tracy Collins and features violinist, Jacob Lawson.