Click here for Part I & Part III

Developing cures for HIV, PKU, and liver cancer with groundbreaking genetic medicines

Jeff Galvin is the founder and CEO of American Gene Technologies, a biomedical company focused on developing and commercializing genetic medicines. Over the past 10 years, AGT has developed a drug delivery platform that targets major lentiviral (from the Latin root lente-, meaning “slow”) diseases such as HIV/AIDS, Phenylketonuria (PKU), and liver cancer. This year, the company will begin a Phase I human trial for its functional HIV cure, potentially solving one of the greatest health crises in the world. According to Jeff, curing HIV is only the beginning for this revolutionary new technology.

Jeff Galvin spoke to Guy Flynn, a partner at DLA Piper, for this interview.

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.

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