Coronavirus Report: The Hill's Steve Clemons interviews Thomas Isett

Steve Clemons: I'd like to welcome Tom Isett, chairman and CEO of iBio, to tell me what the company is working toward and how fast we may get there. Tom, thanks for joining us. And, as I have mentioned to you before, I'm fascinated with the kind of innovative direction that various companies are taking during a time of high health stress for the country. So, can you just tell us very quickly, what are the assets that iBio is bringing to this challenge right now?

 

Tom Isett: Yeah. We've got two that we are bringing forward. … There’s a variety of different types of biological medicines in vaccine platforms that are in preclinical testing as well as clinical trials right now. We are what I would call in a category that I would call of the tried and true, right? So, there's a couple of protein-based vaccine types, one that we have, which is a virus like particle or a V.L.P, and the other is a sub-unit vaccine. So, you're probably used to hearing about the spike protein on the coronavirus. Well, that's where you take a little bit of the protein and expose it to the immune system in order to get a response. And so, we're really interested in both categories because we have a special molecule that we've upended to our sub-unit vaccine. But also on the virus-like particle, there's been a lot of promise and success with that. Basically, you're showing the body a shape and configuration that’s much like the virus itself, with the protein and other sugars on it, and so very durable immune responses have been observed with virus-like protein particle categories. So those are the two main ones, and we're also doing a lot of thorough testing — we have a really big pre-clinical study that's underway, comparing both of those platforms with a variety of adjuvants, so things that could make the molecule better and help the human immune system recognize it and uptake the antigens and create a strong immune response.

 

Clemons: So, I'm not an expert on the timeline of vaccine development. But people I've talked to have said, “You know, we really crushed that schedule down. Lots of other elements are crushing that schedule.” And we've been seeing, I mean, it's almost hard to avoid the horse race right now between those that are in various trials, and we hear that companies like AstraZeneca and Pfizer, Moderna and others that are out there doing these things. But you know, there are more than 400, as I understand it, human trials underway right now. How do you take your assets and your contribution to this and kind of enter that race if you will?

 

Isett: Well, to your good point, look, I mean, vaccine development, I think Merck had record time where they did one in about four or five years, right? So, it's normally a very lengthy period of time to develop a vaccine, and it's critically important, right? Because when it's different than therapeutics, this is a vaccine that you're putting into healthy people. So, you know, of course, we're all hopeful that, you know, all of these vaccines will be successful in human clinical trials. However, there is some benefit, of course, to really focusing naturally on safety, since you're gonna be dosing healthy people, and also get the efficacy as well, and that's why we're taking this extra time to compare the adjuvants and antigen pairings so that we can be more confident when we go into our human clinical trials that the vaccine that we have has the right safety profile and one that can be applicable to, you know, our most vulnerable populations, so meaning, especially, the elderly. So, certainly we've got to be able to move fast. And then, once you've got hopefully an optimized, in our case, vaccine candidate to take forward, you then have to be very ready to go ahead and scale up and make sure that the manufacturing and what you're testing now in these early days in the research phase, is gonna be representative of what you're making and putting into people for human clinical trials when you’re at scale.

 

Clemons: One of the privileges in my job is I get to interview a lot of fascinating people. I've had the opportunity to interview Dr. Anthony FauciAnthony FauciOvernight Health Care: US coronavirus deaths hit 200,000 | Ginsburg's death puts future of ObamaCare at risk | Federal panel delays vote on initial COVID-19 vaccine distribution White House seeks to change subject from 200K COVID-19 deaths Putin calls on UN to strengthen World Health Organization MORE probably about 10 times over the last four or five years. And he worried about this sort of pandemic coming. But it's not only this pandemic. We've seen the flu virus, other things. So, there is this whole equation about manufacturing vaccines that is now getting a lot of attention, and in the past you’ve kind of used eggs. You have other bases for this, which I've never understood. But now, you take a plant-based approach. I'd love to hear what that is about and what are you trying to correct for there? And is this a new thing that we've ever done before? What's our experience with plant-based vaccine production?

 

Isett: That's a great question. Of course, I run the risk of going on way too long on this because I'm an old bio process guy.

 

Clemons: Don't worry, I’ll cut you off.

 

Isett: Thank you. Yeah, that may be required. So, for a really long time, to your point around making vaccines in eggs and things like that: A lot of biological medicines, especially the protein-based types, you have traditionally used some sort of cell, amammalian cell, often times, or even insect cells, and you have to genetically engineer those to get them to make the protein of interest. And so, eggs, of course, are just a big cell. So, there's different ways to get the cells to go ahead and make the protein that you want, right? However, you know the development of that vaccine and making it scalable for manufacturing ultimately can often take a really long time. And you know, you have 14 months, maybe sometimes longer, right? Well, in the case of what we use at iBio with the “fast pharming” technology and why it's so interesting is that that development time gets cut. We don't actually genetically engineer our plants. We grow them for a period of time, and it’s a relative of the tobacco plant. It's a little weed that grows very, very quickly and it puts a lot of its energy into the leaves. And so, a couple weeks into its growth cycle, we get the gene of interest — in other words, program the plant to have it make what we want it to make by actually introducing it via a little bit of bacterium that naturally infects the plant, and it helps take over the machinery. And essentially, you get the leaves in the plant cranking out the protein that you want, so we grow them for a few more weeks and then we harvest them and you just purify the material to get your protein of interest. So, the really cool thing about it, in addition to the speed, is that each plant is what you would call its own bioreactor, right? So, they’re modular in that each little plant makes the protein so unlike other more traditional systems where you have to scale up the manufacturing — so, you move from the small-scale bioreactors; they might be a liters or 10 liters, to these very large 2000-liter tanks that use a lot of plastic and all these other things you know, here, if we want more material, we just grow more plants. And they are eco-friendly to boot, so we're not using a lot of plastic. But importantly, that scale-up process, you know, when you move to those large scales there are certain physio chemical things that can introduce problems. And, you know, “fast pharming” gets to avoid all that because, again, you're just growing it. Each plant is generating molecules that are very representative of each other individual plant. And so, what you're seeing at the research stage is pretty much what you're gonna get.

 

Clemons: So tell me this scale you can get. Because I interviewed Senator Chris CoonsChristopher (Chris) Andrew CoonsMurkowski: Supreme Court nominee should not be taken up before election Battle lines drawn on precedent in Supreme Court fight Sunday shows - Ruth Bader Ginsburg's death dominates MORE the other day and he said, “Steve we’ll come up with the vaccine, we will get some vaccine, but our problem is not the vaccine.” He actually said our problem is not finding the vaccine. Our problem is manufacturing at scale and a large enough level not only to deal with U.S. demand but global demand. Now, I heard you recently in a video that happened to be on your site saying you can manage that, that we can scale up and deal with the U.S. market. So, at what level can a facility like yours produce when it comes to the levels of vaccine we're gonna need?

 

Isett: Yeah, and I'll violently agree with Sen. Coons on the manufacturing and talk about that in a minute. But I think, you know, coming up with the vaccine, too, and one that is safe and really effective and durable, you know, we shouldn't discount that too much. We're gonna get one, someone’s gonna get it. But that's hard too. So, to the manufacturing part. As you actually said in your introduction, the fast pharming facility that we have in the College Station area of Texas was originally built as part of the Department of Defense’s Blue Angel Project back in 2010 and so the entity as part of that project, there was a live fire drill to get the facility up and built in a very quick period of time, which was done in, I think it was about 14 months if I remember correctly. And so, the facility was built very quickly. There was a live fire challenge to make doses of flu vaccine using the technology in the facility, the “fast pharming technology.” You know, we made millions of doses in a few weeks. So, the great part about it is iBio acquired the facility back in 2016 and there's, again, 130,000 square feet of available manufacturing capacity. So, what we ultimately design will be able to scale up. And our own preliminary results right now, our estimates, rather, is that especially with a virus-like-particle vaccine, and this may be true with our sub-unit vaccine candidate as well, we believe that we’ll be able to produce 200 to 700 million doses or thereabouts, right? Like we just talked about before, highly scalable. And then, importantly, too, we're not gonna be seeing the end of our pre-clinical studies here for another few weeks, but, because we're testing with an adjuvant, some adjuvants can have some really important immune response-stimulating capabilities. So, the estimate that I just gave you is assuming that we don't get any benefit from an adjuvant. And if we were to see that, there could be a significant increase to our existing capacity. So, we have the capacity. We’re there. We've got two candidates that we're moving through, and so at least so far is making the vaccine itself, the antigen portion, we've got a straight line.

 

Clemons: I've interviewed a lot of folks involved now with Operation Warp Speed and various folks in the kind of vaccine cultivation driving business either from the testing and production side. I can't imagine that these folks aren't sniffing around your facilities a bit. What is the scene right now with your potential government partnerships? Are they looking or if they haven’t, are they comfortable with the direction you're going?

 

Isett: Well I guess what I wanna say on that is this: I want to share this story because it was really important. So, for an organization like ours, that hadn't been very much, believe it or not, here recently very involved with government and government contracting and a lot of this. Our business model previously had been mostly focused on contract development and manufacturing of other people’s products, other companies’ products. And, you know, it was back in October when we started changing that and moving to more of our own proprietary products while, of course, still doing contract manufacturing for others. And, you know, when the COVID situation started to develop in January, we very quickly said, “OK, well, what can we design?” And, a tremendous credit to our brilliant scientists, we had not one but two candidates, as we talked about. And then four weeks later, we were able to identify that we could manufacture both, so both were viable moving forward. And so, I'll never forget, it was March 12, driving around D. C., trying to meet with senators and representatives. And then also someone took a meeting from us at BARDA and, you know, that’s one of the groups that has funded over many years, technology development in areas like vaccines.

 

Clemons: BARDA here is like THE group. BARDA’s big. So, you hooked up with BARDA?

 

Isett: Well, yeah, and it was literally I mean, we were driving — one of the doctors there, a friend of a friend of a friend somehow knew somebody and they were like, “Hey, would you meet with this guy?” And we will be forever thankful for them eventually passing it along. And we met with one individual there. And because we had our two antigens, we were prepared to just move forward with the antigens alone, right? But because of all the funding that BARDA had done, I had said ,“hey, do you have any ideas on people that you have worked with? Or are there any interesting adjuvants out there because we'd like to perform this study?” And so, they recommended that we reach out to folks at the Infectious Disease Research Institute in Seattle. And the next day we did, and I thankfully, Dr Corey Casper there — a brilliant scientist and leader in the field — took our call, and then, you know, we've been working with them since and the great part was, they had these wonderful adjuvant technologies and tremendous clinical experience, clinical development experience. So, two great things. We're thankful to BARDA for recommending that, thankful to the folks at IDRI they're called, that's the acronym. And then also, too, is we're trying to get ready for hopefully moving into human clinical trials. We had the folks at IBM also with their clinical trials management software. They said,“Hey, we kind of like what you're doing” And they've given us a little bit of help there in that regard, too. So, you know, really, really thankful to the U. S. government and BARDA in particular for that marriage that they helped make.

 

Clemons: Tom, let me just ask you finally — we've only got a minute left. But you know, it used to be that partnerships, particularly in science and manufacturing, we have realities about a global supply chain out there, partnership globally that when, you know, a firm had a partnership with China, or other companies in Europe that was looked at as a strength. Right now, things have become complex, and I know you have some relations with China. Have you had any difficulty in this particular political environment that we have today where nationalisms are rising but yet science is still transnational? So, I'm just interested because you do have a partner in China, I think. Is that a strength or hindrance?

 

Isett: Well, it's interesting … The partner is really as much a client as anything, and it was in a different area. We were partnered with them for a biosimilar as it’s called because you don’t really get generics in the biologics area. And that was in in the space of oncology. So, we were helping them make an oncology medicine for China. Now they had — when the COVID situation broke out, they had come to us with their own vaccine candidate, and we had talked initially about “well let's take a look at that plus the two that we have and see how it goes.” Unfortunately, their particular candidate didn't turn out to be viable. So, I mena I think we're really focused on iBio’s own vaccine candidates. So, these are exclusively iBio’s and we don't really have a partnership per se for COVID-19, other than IDRI.