A national media company, CityBizList, published an interview with Jeff Galvin in a three part “CEO Interview” series. Feedback from viewers indicated that it gives an easy-to-understand background and explanation of AGT’s work and mission. If you are interested, you can view the three part interview below.
Jeff Galvin meets Dr. Roscoe Brady: AGT is born
GUY FLYNN: You have had an amazing career, beginning in some respects with having taught an MIT when you were in high school. Talk to us a little bit about your career evolution from then to becoming the founding CEO of American Gene Technologies.
JEFF GALVIN: What drove me in my whole youth and in my career development were things that I fell in love with. When I was in the seventh grade, I saw a teletype terminal that was donated to our school by Bolt Beranek & Newman, a timeshare company. These things are all ancient terms, which you shouldn’t know anything about—all those things have disappeared at this point—but it was an opportunity to learn how to program computers. I got an independent study at my high school and I learned how to program in a language called Logo. It was my first experience with computers, but I was just smitten. I just loved computers not because I love to program, but I loved what I can see that they could do. I really saw these things as taking away all the rote, boring activities of adding numbers and formatting things, and I could just see an amazing future in these new things that I just experienced—computers.
I was, at that point, 13, 14 years old. My father went to MIT and I’d been to some open houses, so I was comfortable on the campus and I just started wandering around looking for computer resources that I could use. That’s where I got exposed to robots and ADD conversion that would go ahead and allow you to add sensors to computers that can sense the temperature or whatever, and then I realized, “okay, there’s no limit to what computers are going to do.” While wandering around the halls of MIT, I bumped into something called the High School Studies Program and they asked me if I would like to take classes on weekends, because they had people that were teaching classes for high school students in the area. I looked at what they were offering and there was nothing in computer science, so I asked them, “Could I teach a class in programming BASIC. They just looked at me, this little 15-year-old, and they were like, “Well, show us a syllabus.” So, I went home and went to the library and looked up what a syllabus was, and I presented one to them and they liked it. They gave me resources and a classroom on the weekends and I had high school students and college students coming into my class to learn how to program in BASIC. That was my first experience teaching.
After high school I went to Harvard. In the first year I was a very experienced computer person, very excited by it and passionate about it, and so I went through all of the curriculum in the first year, and aced out at everything that you could do in computer science at Harvard at that point. And then I was interested in teaching again, and I got a position as a teaching fellow for Natural Sciences 110, which was the beginning of computer science class—sort of the get your science requirement out of the way if you’re a non-science person—and it was the second biggest class on campus, and I guess I was showing so much passion and excitement and dedication to being a TF that the professor made me head TF. I even got to give lectures to full 1,200 students whenever the professor was out of town and run an organization of about 30 teaching fellows. That was really great experience that I loved.
Again, my whole life I just kept on pursuing what I loved. Next thing, next stop is I get recruited by Silicon Valley. That makes sense with a computer background. I went to HP, and HP really was about the programming, and so it didn’t really light my fire the same way. I ended up shortly thereafter at Apple, and then I got the fire in my belly for computers again. I, probably like a lot of people, had thought that microcomputers were too small to do anything serious, but when I saw what Apple was focusing on, I realized that wasn’t the case—that that was going to be something that had a huge future.
Also, they had an attitude about this thing that really matched mine, which is that computers are tool. They’re not an end in themselves; they’re basically something to enhance people’s lives. Steve Jobs always called it “the bicycle for the mind,” and that was the way that I felt about computers. You don’t have computers because you just like computers. You have computers because they do things for you that are worth a lot more than you spend on computers, and utility and accessibility and usable power was what Apple was all about.
Anyway, that lit my fire in terms of entrepreneurship. I had a couple of startup companies. Some of them did well; other ones didn’t lose so much money that it undid the ones that did well. I was in Silicon Valley investing in real estate as well, and I ended up retiring at about age 40, 41. If you can imagine this, I got bored of leisure time and I wanted to dabble again. People found out I had money and I started getting business plans over the transom—potential investments—and that sounded like a good way to get back into business without being 24/7 again.
One of the things that I got was an introduction to Roscoe Brady at NIH. He showed me viral vectors, and I immediately had the same excitement and vision for a future of viral vectors that I had the first time that I saw a computer. I fell in love with it and that’s what driving me right now. I think this is an amazing technology: the utility for human beings, the potential of improving people’s lives—of mitigating diseases that heretofore were completely unaddressable by traditional drug development. It’s all there. Ten years ago I could see it, the moment that Roscoe Brady explained to me what viral vectors could do. I said, “This is the operating system for the human computer.” The human cell is nothing but an organic computer to me. Runs on DNA, which is coded in ACTG—that’s not that different than computers that run in binary, which is coded in 0s and 1s. You can think of ACTG as base-4. It’s all just numbers, and these genes are just commands to the machine. And if we can change those commands, we can change anything. If we can get in there and we can work on the DNA, I know that’s a source of a lot of problems and it’s also a solution to a lot of problems. I saw this amazing future clearly laid out in front of me and I just had to get involved, and that’s what’s driven me for the last ten years, and that vision is really playing out.
GUY FLYNN: Tell us a little more about Dr. Brady and his amazing background as a scientist, and how the two of you came to co-found AGT—and a little bit about your relationship personally with him.
JEFF GALVIN: Dr. Brady was an amazing man—just brilliant, recognized in the field, highly decorated—even a commercial success. He was the person who discovered the root cause of Gaucher’s disease, which is a horrible disease where people cannot metabolize lipids in their organs and their organs swell over time and they burst, so they die of basically organs that just swell up with lipids that can’t be processed. He discovered that they were missing an enzyme called glucocerebrosidase. He figured out a way to get it back into the necessary cells, and he made a cure for Gaucher’s disease, and out-licensed that to Genzyme that sold a billion dollars a year extending people’s lives with this new technology. In terms of a scientist, [he was] an amazing guy, an amazing researcher, and incredibly passionate about helping people.
I’ve got to say, personally, he’s just the most down to earth and gracious person you will ever meet. He didn’t know me from Adam, and I walked into his office and he just treated me like I was a some sort of peer and he was going to explain to me what he knew. And he explained it so well that it was easy for me to understand it right away and I just said to him, “Somebody’s going to have to be the Microsoft to this industry. It might as well be us.”
Now he was retiring, so he couldn’t really jump into something full-time. He was already I think in his late 70s when I met him, and so he wasn’t going to kind of go back to the bench and go to work and be that kind of co-founder, but he was a cheerleader. He was our inspiration. He was somebody that gave me great confidence in the future of viral vectors during those early years, and he supported my vision for what this could become, as well as always lending a guiding hand whenever he could. He’s still a continuing inspiration around the company and we miss him greatly. He passed away June 13, 2016—a big loss for the community and especially for us, but we’re going to continue the work that he started at NIH. I think this is going to turn into something really amazing and important and significant, and he was a big factor in that.
How gene and cell therapy will change the world
and disrupt the pharmaceutical market
GUY FLYNN: Talking little bit about viral vectors as a concept, and you said “viral vectors are the operating system for the human computer,” it seems to me, and to a lot of people, that this technology has an enormous disruptive potential—if not reality. Talk to us a little bit about where that disruptive energy is heading and its magnitude, potentially now and into the future.
JEFF GALVIN: Yeah, that’s a great question. Think about the drug market as it is today. It’s roughly a trillion dollars a year in pharmaceuticals that are being sold. And a lot of these things are high value. If you go out and you buy a bottle of aspirin, you get really good utility out of those aspirins. You get a bottle of 500 for 10 bucks or whatever, but nobody complains about the price of an aspirin. You take one, doesn’t cost you very much, it solves your headache, it reduces fever, it reduces inflammation, it does something valuable, and it doesn’t have many side effects. That’s what I consider not just a good drug but a high utility drug.
Now, there are drugs that I don’t consider to be high utility because they don’t give you a lot of value for your money. There are a bunch of different treatments out there that are sort of end-of-life treatments. They might extend your life by a month or two. They cost a hundred or hundreds of thousands of dollars. In those cases, I think that it’s questionable whether it’s a sustainable model that those things can be sold to everybody that needs them, especially if the number of people need them—like in a cancer application, where maybe this is one of those things that you throw at cancer in the final stages to give you a month or two—well, can we afford that for everybody in the world? I don’t think so. That’s where I think the disruption is going to take place.
What are the factors? The factors are, number one: Gene technologies are much more powerful and much more targeted than former ways of developing drugs or former drug modalities. This is the power of this industry that’s going to be disruptive, in that we can go ahead and we can have a much greater effect with a much smaller side effect, and that has to do with the specificity of gene technologies, and also the targeting of gene technologies. We can go ahead and make these things act in just certain cells in order to limit the side effects. Now, a lot of drugs are just out of the market because of side effects.
A great story is the story of the development of Viagra. They were developing a blood pressure medication and it didn’t work on blood pressure, but it had this weird side effect and that side effect then became marketable. It even got a disease founded in its image, which was just considered old age at one time—or other rare conditions that would lead to it—but now is a giant industry. The side effect of Viagra turned out to be something that people thought had good value, and it turned out that even though you take this drug and it goes all over your body and that it was intended to have something to do with blood pressure, it doesn’t have too many side effects—and as a matter of fact most of those side effects have to do with blood pressure.
That’s the thing: the old mode of drug discovery, also because it’s untargeted, because you have to put something in the whole body and then you hope it works on the cells that you intended it to work on in a positive way without having too many side effects in the cells you didn’t intend it to work in, it’s almost luck when you discover these drugs. In gene therapy it’s not that way. We’re reprogramming molecular pathways in your cells by rewriting your DNA. And we can do this in a very specific targeted manner so that we have a good sense that the side effects will be limited. We can ratchet up the therapeutic index—what does that mean? We can go ahead and use very, very powerful things on the target cells, knowing that they won’t act on the off-target cells, and therefore that power won’t lead to some powerful side effect that will knock them out of the running. Over time we can develop these things more efficiently, because what happens is is that we find things that work and we can reuse them from drug to drug.
One of the things that I tell people is that every drug that we make is 80% some other drug that we’ve done already. We start off way down the path. You can imagine why that is. If we have gene X and we’re expressing it in cell A and we decide we want to express gene Y in cell A, we just go ahead and take some existing vector that we already developed that had all the software to do it exactly how we want it to, and we chop out gene X and put in gene Y—and now we have a new drug. So, the cost of our drugs have been falling precipitously. I mean you can’t imagine that we’re at about one-twentieth the cost of our original drugs over 10 years. The development has brought the cost of development down by a factor of 95%—and the time to develop them down by almost that amount as well, by 90% to 95%.
What that means is that we can turn out viable drug candidates that we designed that had less likelihood of side effects, and which actually have the effect that we designed them to do, very quickly and inexpensively. We can test them in cell models and get a go or no-go decision very quickly, maybe within $50,000. If we decide to progress it from there, we can get the first human efficacy within about a $10 million investment. First human efficacy is where a drug company can de-risk that. In other words, a pharma company can look at something that has first human efficacy and say, “Okay, now we know what the market is and what the clinical path is, and we know that we can invest in this and actually commercialize it.” It’s sort of a biotech dream to be able to now do these things at a fraction of the cost of traditional drug development—because remember that drug candidate that I just I told you about, which might take us a couple of months and $50,000 to do? Well, in traditional drug development what you do is you randomly make about 10,000 new molecules and then you’d screen them down—and this would be where your technology is, you could come up with some really good screening procedure to get it down to two that are worth testing, and maybe progressing that into a mouse—and that would take you two years and $10 million. In two years and $10 million, we can get from idea all the way to first human efficacy.
Now let’s look back at this drug market. About half that trillion-dollar market are things that I would consider low utility. These are going to be replaced by highly effective gene therapy and cell therapy drugs. When was the last time you saw $500 billion slosh from one place to another? This will all happen in probably a decade to a decade-and-a-half. We’re going to create a bigger market than the computer industry almost, within that amount of time.
This is bigger than computers. It’s bigger than the internet. People don’t realize what a revolution this is. They don’t realize it’s happening right now under our feet, right before our eyes. A surprising number of people have never heard about gene and cell therapy and have no understanding about how this is likely to impact their lives.
There’s going to be a look-back moment, which is probably only about 10 years from now, where you’re going to say, “How did we ever live without gene and cell therapy?” But you’re really going to mean it. It’s not going to be how like when you look back now and go, “How did we ever live without the internet?” Because you could live without the internet. But if you have a 4-centimeter tumor in your liver, you literally would die without gene therapy—because I think we’re going to be testing a cure for liver cancer in 2019. That’s how fast these things are coming on. and so, there’s going to be a moment 10 years from now where you’re not only saying, “How did we live without gene therapy?”, but you’re going to be telling your kids and your grandkids, “We used to use radiation and chemotherapy to treat cancer. Can you believe that? We used a beam ionizing radiation, cancer-causing radiation, through your body in order to cure cancer.” That’s going to go the way of bloodletting in leeches, I promise you. That’s what the public has to look forward to in the next decade.
GUY FLYNN: Well, that’s quite a future for humanity. Just to talk a little bit about the ethics of where this technology is heading—and we’ve had a chance to talk about this a little bit in other conversations—we may be talking now about a future in which people live largely disease-free and thereby are living for much longer periods of time. What safeguards, if any, do you think need to be in place or is the industry putting in place to make sure that the technology doesn’t overrun the capacity of humanity to absorb the byproducts of these advances, such as having many more human beings living for 50% longer, and the effect on natural resources that might introduce?
JEFF GALVIN: I would say that that’s probably a concern that will start to become apparent in the next few decades. I think we are going to eliminate a lot of the terminal cancers, I think we are going to mitigate a lot of serious diseases, and I think we could go through a decade where almost nobody dies, except for old age like massive organ failures, car accident—things like that. Population growth could become a concern. I can’t say that I have an answer for that, but I also know that technology doesn’t stop. The toothpaste is out of the tube—it’s been discovered, it will be actioned. There will be benefits, there will be challenges. I think the benefits will greatly outweigh the challenges.
One of the saving graces of what we’re doing is that the costs are dropping. I mean, you understand Moore's law in computers, but if you look at the cost of sequencing, it’s dropped much faster than Moore's law. And that’s not a bad indicator about how this whole industry is going. You will be able to experience some of the benefits of these cost efficiencies over time that distribute this power broadly in an effective manner. I think it’s less likely that it will become something where we can’t afford it for people, because I think that it’s going to get cheaper and cheaper over time, just like computers have gotten cheaper over time, and they’ve gotten smaller and they ended up in your pockets, and who would’ve ever thought that—that you would have four thousand times the Apollo program in your pocket, and you could talk to it? That it would understand you and transcribe it and they answer things for you? That’s the way gene therapy is going to be.
I compare it to the computer industry all the time, but we’re really at the punch card or paper tape days of talking to computers—to the human computer—and that’s what the viral vector is. It’s like the paper tape in this industry, and the operating system is all the tools that we have developed that we can put on these paper tapes to make these computers do amazing things. I think that the future of gene therapy is extremely bright. I think it’s going to come on faster, and it’s going to drop in cost faster, than even computers did. And my theory for why that’s happening already and why it will continue to happen is because the computer revolution is helping to drive it. We’ve got a previous revolution and we’ve got this huge ability to churn data, and to automate processes, and to control instruments and manufacturing of these new genetic drugs, and that’s bringing efficiencies to this new revolution that the computer revolution didn’t have. That’s why it only followed Moore's law. Can you imagine that? It could only achieve Moore's law.
How AGT is using HIV to cure HIV!
The future of gene technologies Part 3
GUY FLYNN: You’re particularly involved with HIV, and I’m going to quote you again on a couple of aspects of that: “AGT hijacks the hijacker, re-regulating gene expression to mitigate disease, using HIV to cure HIV.” Talk to us a little bit about where the company stands with respect to HIV, and what the technology is—and what the effect of the technology is on the HIV disease.
JEFF GALVIN: Let me go ahead and tell you how we’re solving HIV. If I start it from the beginning about how viral vectors work, I think it’s a very interesting story that anybody can understand, but it really cuts to the core of what gene and cell therapy is. HIV is a great example of that.
This is going to blow your mind. These viral vectors that we are talking about, specifically something called the lentiviral vector, which is what most of our technology is based on, is derived from HIV—human immunodeficiency virus. Now, on one hand it’s this horrible, scary virus. On the other hand, it’s an incredibly clever delivery mechanism for a genetic payload, which is the disease. What scientists have discovered—and what viral vectors is all about—is we can now take any virus, really, we can crack it open, we can scoop out the disease, and we just end up with an empty delivery vehicle. It still has that same ability to install genes into your cells, but is no longer carrying a disease. HIV isn’t HIV—that’s why we call it a lentivirus. It’s basically the delivery capability of HIV with AIDS erased. The other thing that we erase from it is we erase its ability to replicate, because for safety reasons when we make a virion, we don’t want it to get into your cells and produce additional virions. We want to be able to treat you with enough virions to go ahead and change your programming in the cells that we want to get to, but we don’t want to risk this thing starting to replicate, moving all over your body or even escaping your body. You could potentially start a new virus that way.
This is extremely safe, what we’re doing. We’re modifying HIV so that there is absolutely no way that you could get AIDS from it, and there’s no way that it could create a new disease, but we’re preserving in it that allows us to go in there and implant new genes in your DNA, just like HIV does.
Well, what kind of genes can we put in there? We could just put in a gene that you’re missing. There are a lot of diseases out there that just boil down to that you’re missing some enzyme or some protein that is made by a specific gene in your DNA and that gene in you is defective. We call those autosomal disorders. They’re usually inherited diseases. You just have the inability to make this particular protein. It could be something mildly inconvenient like lactose intolerance, or it could be something really serious like hemophilia or beta thalassemia or phenylketonuria—things where it’s a huge painful disease to have, sometimes even deadly.
But it all boils down to the same thing: you’ve got a gene that is not doing what it’s supposed to do. What’s the simplest application of having this delivery vehicle that can deliver anything? We just go ahead and get one of those genes pop it into our empty stealth bomber of a hollowed-out HIV capsule, piece it together—we have to replicate these things, that’s our manufacturing process—and then we go ahead and treat cells in your body, and guess what? You start making that gene product. And if you now have the enzyme, or you now have that protein, that disease might go away. That’s the theoretical basis of what we are doing.
Now, these genes that we put in there could be genes that we turn on, like I just described to you, but they can also be genes that are synthesized to make what are called short interrupting RNA—siRNA. What those things do is they can bind with the messages from genes that you do have and effectively shut down those genes, so we’re not cutting that gene out. Let’s say you’ve got a gene that’s driving a disease state—cancer is actually oncogenes that are turned on—we could shut off that oncogene by putting an siRNA to that oncogene message, and effectively it turns off that gene. Essentially, within this delivery capsule we can put something that either turns on a gene, up-regulates a gene; or turns off a gene, down-regulates a gene. We can edit your gene expression. It’s incredibly powerful, so we can shut off things that shouldn’t be firing, like oncogenes, or we can turn on things that should be firing, like the phenylalanine hydroxylase that you need to have so that you don’t develop the disease phenylketonuria.
This brings us to HIV. What is HIV? It’s AIDS genes that are implanted in your cells, and this is where originally I got the idea that, “Hmmm, maybe that delivery capsule since it can down-regulate genes—could we down-regulate those HIV genes?” I asked one of our PhDs and it was like, “Sure, why not?” The other thing that I had learned about HIV is that the entry point on your T-cells for the HIV virion is something that requires a surface receptor called chemokine receptor number 5—CCR5. They know this because there are certain people in Europe that are born immune to HIV—they can’t contract HIV—and it ‘ because they have a rare disorder called delta-32 mutation, but basically that is just fancy talk for some reason they are born without working alleles that make CCR5. Their T-cells are absent, and since the HIV virion needs to hold onto CCR5 in order to penetrate the T-cell, when it doesn’t have that handle, it can’t get in. So, that was the next thing I asked the PhDs. When I read about that, I was like, “Could we shut off CCR5 in T-cells?” They were like, “yep,” and I said, “Would that actually get rid of it off the surface?” Yeah, it turns out that if that gene is not firing in the T-cells, then those CCR5 receptors on the surface of the T-cells will go away, so we can simulate a delta-32 mutation in anybody.
Well, that’s our drug. We shut off the HIV genome by down-regulating conserved regions of HIV. If a cell that we go into has HIV, it can no longer function, so it can’t make more HIV virions. And then, even if there are cells in your body that are not making HIV virions, they can’t get into T-cells. What we do is we take out a little bit of your blood—actually, only a half a liter or even less than that: 400 milliliters of blood—we do what is called a leukapheresis, and that is we strain for all of the T-cells. Then, we amplify—it turns out that even if you’ve never been exposed to HIV, you have HIV-specific T-cells that are waiting around like a flu T-cell or a cold T-cell that you’ve never seen the flu or the cold—it’s waiting around because you have this infinitely diverse set of T-cells that are prepared for almost anything. We take out those T-cells and we amplify them, so we have more of them, and then we treat them with our lentiviral vector to erase the CCR5 off the surface, so they can no longer be penetrated by HIV.
Why is it that HIV ends up taking over your body? It’s really simple: The T-cell that was designed to wipe out that HIV virion, while it’s trying to eat that virion, the virion infects the T-cell. It becomes the beachhead for the infection because in fact that T-cell, now having been excited, goes back to your lymph nodes and replicates. That spreads HIV all over your body. Now, it can take its time taking over the rest of your T-cell population. Now, if we go ahead and we take somebody that is well controlled on antiretroviral therapy, guess what? They have HIV-specific T-cells again. So, you would say, “Why aren’t they immune to HIV at that point then, if they’ve got T-cells that are all ready to go?” Well, as soon as you withdraw that antiretroviral therapy, one of those T-cells will meet a virion and the viremia will rebound within 21 days, which is the normal rebound. Why is that? Because that virion will just reinfect that HIV T-cell, it will deplete those HIV-specific T-cells again, it will utilize that T-cell to spread around the body, and it will completely re-infect the patient. We take these people that are well controlled on this antiretroviral therapy, they have those HIV T-cells—and we’ve tested this, we know that they have them; we already have blood in our labs where we’re processing the blood—and we’re able to get them to a critical mass of HIV-specific T-cells that are impenetrable by the HIV virion, and they are therefore rendered immune to HIV for life. That’s the HIV cure in a nutshell, and it all comes down to the fact that we can down-regulate the HIV genes, and we can down-regulate the CCR5 gene, and we can re-program these T-cells to be impenetrable by HIV, and we can remove the one advantage that HIV used to have over your body.
GUY FLYNN: Now, is that conceptual revolution that you dreamed of and came up with specific to HIV, or is that replicable theoretically to other diseases?
JEFF GALVIN: It’s absolutely applicable to other diseases. Now, of course, when you look at AGT’s platform, we have the HIV project, which is an infectious disease. We believe that there’s a whole bunch of different infectious diseases that can be treated this way. We might go after hepatitis B or HPV, Ebola, Zika—there are a lot of different ways that we can enhance the immune system in a safe way, where we could render you immune to certain infectious diseases. We think that that’s got a future, but HIV is already a big accomplishment in that area, and that’s going to prove out the whole platform.
But the platform—there’s more to it, because our ability to re-regulate genes also works in these autosomal disorders. You know how many incurable autosomal disorders are out there? Somewhere between 7 and 10 thousand. Did you realize that 21% of the morbidity in the healthcare system is attributable to these monogenic diseases? We’re spending 20% of a 10 trillion dollar market just on palliative treatments for people that have these autosomal disorders. We’3re doing our first autosomal disorder as something phenylketonuria. We’re replacing this phenylalanine hydroxylase gene. And it’s more complicated than just replacing it. It turns out there are some nuances—and I call this the creative and engineering aspect of what we do, because we take this basic technology and then we solve some problems along the way—just like if you are building the Golden Gate Bridge: yeah, you can have a great plan, but you encounter a whole bunch of challenges as you’re actually putting up those towers and stringing those wires, and this is what the engineers solve to really make that bridge come alive. Well, we’re making bridges to these cures the same way. And that’s the way that our PhDs look at themselves. They look at themselves as sort of artists, creative artists coming up with new ways to combine these technologies to address what we call low-hanging fruit in disease categories, and then they’re engineering has some of the problems that you inevitably encounter as you try to actually build one of these bridges to a disease cure. So, that’s going to be our first in the monogenic category, but you can see that has a huge life ahead of it as well, so that’s another big area for us.
The last area for us is immuno?oncology. Immuno?oncology is the idea of getting your immune system to turn on the cancer—in other words, to be more effective against the cancer. There are a lot of approaches to this, but we have a really unique one that we call Immunotox. Instead of treating your immune system and hypercharging it to go after cancer—and that’s what CAR T is all about—we treat the cancer to lower all its defenses against your natural immune system, without even treating the immune system, and then we convert that cancer into a little factory that creates stimulatory peptides that actually increase the attractiveness of the cancer to your immune system and stimulate the natural specialized cancer surveillance cells that are clearing cancer from your body every single day. In reality, everyone walking around has some cancer, but we don’t call it cancer because it’s a natural occurrence in cells where they will actually just get so stressed out that they’ll turn cancerous and then the specialized immune cells eliminate them like they’re nothing. As a result, [there’s] a normal immune system and a normal amount of this cancer occurring in your body, and you would never actually get what we tend to think of is cancer.
What we think of cancer is when the immune system gets a little bit behind the cancer and it grows to a critical mass point where it gets to a condition where it can’t be handled naturally. In fact, when it gets to that critical mass point, the cancer is very clever and evolved. What it does is it actually has ways to camouflage itself against those immune cells that would have normally eliminate it when it was a 1- or 2- or a 3-cell occurrence. It puts out what are called checkpoint inhibitors—a famous one is PD-L1, and there’s a very well-known drug called KEYTRUDA, which blocks that PD-L1 receptor and so it doesn’t fool your immune system into thinking that that cancer is what? The cancer makes itself look like an organ in your body. It utilizes something that your heart utilizes also to make sure that your immune system never goes after your heart. And so when you block that PD-L1 in the cancer, voila! That cloaking is gone and at least the immune cells can help in your cancer therapy.
In what we’re doing, we’re not just dropping the camouflage_dropping the cloaking—we’re putting a neon sign on this thing and saying “free lunch here” to the natural part of your immune system. You know what we’re finding in the animal tests? These specialized immune cells will eat the cancer at 300–600 times its normal rate. That primary tumor just melts away.
And here’s the kicker: These immune cells have to circulate to your lymph nodes in order to replicate and bring back an army of themselves to fight that primary tumor. Guess what they pass on their way back and forth? The metastases and the secondary tumors. And we’re seeing evidence that it cleans them up as well. This concept that we’ve developed and patented may be a natural and safe way to treat even late stage cancers.
This is what my hope is. I think the first application of this is going to be in liver cancer, and I hope what we’re going to find is that we can melt away those liver tumors and get rid of the metastases at the same time. The primary tumor goes away and we find out that it doesn’t just all of a sudden and pop up somewhere else, because these natural immune cells in this highly stimulated state that are circulating all over your body—they’re enough to clean up all of those things. As a result, you might get five extra years of life out of maybe a $100,000 treatment that formerly a $100,000 would have only bought you a month or two. Now five years, that’s good utility, right? This goes back to my original point in why this is so disruptive.
GUY FLYNN: Now, people watching this program are going to want to know: How quickly to market are these technologies? In terms of clinical trials, talk to me about the clinical trial timeline for the HIV aspect and for some of these other diseases that AGT is working on.
JEFF GALVIN: HIV is the lead for us right now. Our three projects are HIV, phenylketonuria, and liver cancer. HIV had its pre-IND meeting last year, and the IND document, which is everything we agreed on with the FDA to provide to them to evaluate the safety—or to prove the safety, because we pretty much approved it with the data that we gave them in the pre-IND document, but we have to re-prove it with clinical grade materials in a very formal style; that’s what the IND document is—we expect that to go in at the beginning of the first quarter of 2018, so in about four months from now we think that that will be submitted. The way that the FDA works is that document is the agreement that we came to a year ago with them, and so they have 30 days to evaluate that and see that we actually provided everything that we promised and that they specified. In fact, if they don’t object, they don’t have to actually send us an approval at that point. If they don’t send us a notice, within 30 days, saying that “we found something wrong,” we’re free to start our clinical trials. That’s probably going to be middle of the first quarter.
We will be able to get safety data out of this within a matter of months and I think efficacy data within a matter of months after that. By the end of 2018, I hope to be able to come back to you and show you a cohort of cured HIV patients. In other words, people that had HIV, who no longer have to take antiretrovirals every day, have no chance of developing AIDS, have no chance of spreading HIV to anybody else, and are immune for the rest of their lives—so they can’t even re-contract it. They’re actually better than cured; they’re permanently immune, like you expect to be from the virus. That’s very exciting. That’s all going to happen. I think you’re going to see a lot of news on that by summer of next year.
We’re looking at preliminary data because we already have a clinical trial site contracted. We’re already getting patient blood that we’re putting through the entire treatment protocol. The only thing we’re not doing so far is re-infusing it into patients. We know that there’s this critical mass point of protected, HIV-specific T cells—that, when it’s in your body, gives you immunity to that virus—and we’re exceeding that by manyfold. We are feeling cautiously optimistic—or I could say, since I’m not the scientist, I’m feeling extremely confident—that we’re going to have a good outcome to that study.
Now, PKU and in hepatocellular carcinoma, commonly known as liver cancer—we expect to have the pre-IND meetings in 2018, then get the INDs out, and get into the clinic in 2019. Those two drugs are sort of other bullets in the gun, and that was part of our strategy: we didn’t want to bank on one thing in case we hit some hiccup. Keep your fingers crossed we won’t hit a hiccup on that, but these other diseases are looking equally good in terms of their path to the clinic. It’s just a matter of how much resources do we have to progress things all in parallel. Those things are looking very promising as well.
GUY FLYNN: So Jeff, my last question for you has to do with safety, and part of your answer has probably been subsumed in some of your other answers, but viral vector safety—is this is ultimately a safe technology?
JEFF GALVIN: I believe it is. And the reason that I believe it is is that viral vectors have actually been around and have been used now for about 40 years. In fact, lentiviral vectors are on third- or fourth-generation depending on who you talk to. Call them third-generation lentiviral viral vectors. They’ve had a huge amount of experience in the clinic. They’ve had an even much larger amount of experimentation in laboratories around the world. The basic building block of the lentiviral vector, when properly used, I think is very, very safe. I think its safety has been largely established. and now it’s a matter of “Are atoms safe?” It depends on how you use it, right? Radiation leaks? Not so good. Every powerful technology needs some maturity in order to utilize it within a safe zone and I think that there were some early misfires in viral vectors, where people were over exuberant with this new toy and they used them in manners that they didn’t really understand, and it led to some adverse consequences, which actually threw a pall over this whole industry in the late 1990s and the early 2000s. But we’re in a more developed, more matured technology,—and matured in terms of our use of that technology—phase of this, and I feel that it’s very safe.
There are several hundred gene therapy trials on clinicaltrials.gov right now. There’s a variety of different viral vectors that are all safe in different types of uses. I don’t see anything out there that I feel is really—not that I’m an expert in this, I mean you would really want to talk to PhDs that are at the heart of this research to say “Is anybody doing something that is pushing the envelope too far?”—but I’m very comfortable about how AGT utilizes viral vectors, and I think that we’re staying well within that practical zone that is well understood and safe.
GUY FLYNN: AGT really is at the forefront of personalized medicine, wouldn’t you say?
JEFF GALVIN: Depends on what you think of as “personalized medicine,” because people use that term in a variety of different ways. In one way—and I think what’s really getting the most gravity or traction in terms of personalized medicine—is the idea that by getting information about you, your genomics, we can determine which existing treatments are most likely to work for you. Where does AGT fit into that? Since we don’t have an existing therapeutic, we might not really fit into that model, but I think that what you’re going to see is, coming out of this whole revolution in big data in genomics, you’re going to find a lot more information about the underlying drivers of disease, which we can action on viral vectors and we can start to create new therapeutics. It doesn’t matter if you take a genomic test and it tells you that you have a 30% greater chance of having disease X—if there’s nothing you can do about it besides worry. The key to really actioning this whole idea of genetic medicine—of personalized medicine, in my mind—is this amazing geometric growth that I expect to see in therapeutics that are based on re-regulation of genes and editing of genes, and really all of the genetic technologies that we’re at the forefront of, but still really at the beginning of a road of discovery and development that will ultimately make what we’re doing right now look pretty crude.
GUY FLYNN: Phenomenal. Well, Jeff this has been a terrific discussion, and to many people this sounds like the stuff of science fiction, but guess what? The future is now in many respects. We wish you all the best with AGT and with all the tremendous, groundbreaking work that you and the company are accomplishing. Thanks for your time.
JEFF GALVIN: Thank you.