American Gene Technologies (AGT) is a cutting-edge biotechnology company creating technologies that speed up the development of cures and treatments in the emerging field of gene therapy. In this interview, founder and CEO Jeff Galvin pinpoints the current challenges in drug development and offers a unique perspective on the future of medicine.
Please describe what American Gene Technologies is working on these days.
Our lead program is a cure for HIV, which is currently in the clinical stage. We already revealed our first safety data, which indicates a high probability to cure HIV. We don’t want to make any premature promises, but there’s a lot of good data, leading up to this point, that gives us some confidence that an HIV cure may be in reach even with the current clinical trial.
Our second lead program is in monogenic diseases such as phenylketonuria, a rare disease that is epicentered in the Middle East. In Europe, about one in 10,000 babies has this condition and in the United States, it’s about one in 13,000. They’re born with one broken gene which causes them very serious problems throughout their lifetime. We have a gene replacement drug that looks very promising for people with this condition.
One of our proprietary immuno-oncology assets allows us to stimulate the natural Gamma Delta T-cells in your body to clear solid tumors of the epithelial type, such as breast, prostate, lung, liver, colon, kidney, ovarian, pancreatic, head and neck, and skin cancers.
In the United States alone, 900 people per day die of those solid tumors. One shot of our proprietary viral vector into the primary tumor stimulates the natural immune system to attack that type of cancer in your body.
Everything in your body is invisible to these types of Gamma Delta T-cells, except for malignancy. So when you stimulate them, they can’t attack the wrong things. They will selectively pull all of the malignancy out of your body. That means it gets the primary tumors, secondary tumors, and metastases.
We already have a 1000 mice study in advanced-stage cancers. We use human Gamma Delta T-cells in the mouse, and when we inject one tumor, they all disappear. It looks very good for the stage that it’s at. The preclinical animal data is very encouraging. We are working on this in collaboration with Stanford Medical School. We may be able to greatly improve outcomes on deadly solid tumors.
We’re not the only company in the world that’s modifying DNA for better health, but we have the broadest platform with the largest selection of tools, which makes it the quickest and most reliable way to address a new disease. In the future, we’ll be making new drugs at a fraction of the cost and time it takes today.
Here’s a quick video introduction to AGT:
What are some known applications of gene and cell therapy?
People with deadly terminal cases of acute myeloid leukemia and lymphoid leukemia are already being treated with CAR-T, which is another form of cell therapy.
There’s a cure for ACA skin, kids that are born without immune systems. They pick their bone marrow or replace the missing gene, and they give those kids an immune system. Some of these patients were living in plastic bubbles because, without an immune system, the tiniest bit of bacteria or virus would kill them. They’re now out of their bubbles thanks to gene and cell therapy.
There’s already a cure for a form of blindness that came out of gene and cell therapy. It’s not ours, but it shows you the power of this technology. They replace one gene in the eye of people that were blind due to Leber congenital amaurosis and now, they are seeing again. Some kids that were blind are now hitting baseballs, and adults that were blind are now driving cars. It’s miraculous.
There’s a cure for spinal muscular atrophy, a deadly childhood disease where kids don’t even live until age 4 because their spine doesn’t form normally. They can’t lift their head or roll over, they never learn to walk, and they eventually die because they can’t breathe on their own. That is now curable thanks to a drug that was brought out by a company called AveXis.
Two forms of liquid cancer leukemias were completely incurable in the past; they’re now 60 to 80% curable thanks to CAR-T. So this is very exciting. AGT is all about bringing efficiency to the development of these drugs.
How is this different from Western medicine as we know it today?
When you swallow a pill or get a shot of medicine into your vein, the medicine would go everywhere and act on every cell it gets to. Traditional drugs may be very powerful and effective at curing a disease, but they have side effects on cells that don’t need them.
With many drugs, they either have to ratchet down the power of that drug to avoid intolerable toxicity, or the drug may be disqualified entirely because it affects some very important cells in your body. Even though they might cure your disease, they could also be debilitating or deadly. With gene and cell therapy, you can edit the DNA and shield those healthy cells to administer the drug safely by “targeting” the change to just the cells that need it.
Think of it as an update to your computer. We’re converting human viruses into human updates. We can put a gene in you that you didn’t have before. People who were born missing a gene, or got a bad gene from both their parents, may have one of 7,000 known monogenic inherited disorders where you’re not making an essential enzyme or protein. For example, phenylketonuria is caused by a missing gene called phenylalanine hydroxylase.
Genes are just amino acids and nucleotides in a certain sequence that forms an instruction to your cell. The industry is so advanced now that you can order any human gene or synthetic gene online, and it’ll come by FedEx the next day.
We crack open a virus, “scoop out” the original “bad stuff” that was inside, put that new gene inside, and test it on a cell model in a cell culture hood, to see if the gene is expressed. If so, we can develop that into a gene replacement drug.
It turns out that viruses, COVID included, only go to places where you have an ACE2 receptor, such as the respiratory tract. The spike protein knows how to target and bind with those receptors. That targeting capability can be utilized to bring the drug just to the cells that need it. We can look for a receptor that’s common on the cell that we need to treat, and then we put proteins on the outside of the viral particle that will bind to the cells that we want to get to.
Do you see how targeted that is? It’s very much like a monoclonal antibody because it works the same way, but we can take it even further. Once the drug infects the cell, we can put an on-off switch on the drug itself, which will determine, based on the enzymes or proteins that are already in the cell, whether the cell has a specific disease, and only turn it on when and where needed. It becomes an if-then statement. It’s like software for your body. And it means that we can isolate the effect only to the cells that need it.
This technology is more powerful because it goes right down to the root drivers of the cell. It’s more targeted because we can narrow it down to just the cells that need it, and isolate you from a lot of the other side effects that could come from treating cells that don’t need treatment. And it is very specific, so we’re either turning on a gene or turning off a gene, so we’re making a very specific change.
We’re going into an age of very specific, predictable, targeted, powerful drugs that are going to revolutionize pharmaceuticals. AGT is proud to be on the cutting edge of that whole industry.
The way I see it, in the next 20-30 years, nearly everything that threatens human health will be gone. Imagine getting breast cancer or prostate cancer and being cured without surgery, radiation, or chemotherapy. You’ll just get a shot and it will all go away naturally. They may image you with ultrasounds, MRIs, or X-rays, just to make sure it’s all gone, but that would be it.
Radiation and chemotherapy belong to the past. These targeted therapeutics I mentioned are likely to eliminate cancer once and for all.
What can you tell us about your new treatment for HIV?
HIV’s strategy is to infect the T-cells that detect it. We pull out those T-cells and modify them with our proprietary lentiviral vector to shield them against infections. When a normal T-cell becomes uninfectable by any virus, it can effectively clear that virus.
Some people are immune to HIV because they have a rare mutation where the virus can’t get a hold. With normal people, if the virion floats in the bloodstream for a couple of hours without hitting a T-cell, it will die. That’s how fragile the virus is, but when the T-cell tries to kill it, the virus grabs on and merges with the T cell’s DNA.
Now, the sentinel T-cell that is supposed to protect you becomes the beachhead of the infection. It replicates the infected DNA and spreads HIV in your body, instead of fighting it.
A simple cold virion has no capability of infecting the T-cell. When the cold T-cell comes along and finds the cold virion, it does exactly what it’s supposed to do: kill the virion and replicate the T-cell to create more “soldiers” against the pathogen. That starts an entire immune cascade that will eventually clear your body of the cold.
Once we take HIV-specific T-cells and protect them from HIV, they will be able to clear HIV just like cold-specific T-cells clear a cold. That’s how we make people permanently immune to HIV.
We recently published an article with the National Institute of Allergies and Infectious Diseases. Anthony Fauci, the head of this organization, has been known in HIV research long before COVID came along. His lab duplicated some very exciting preclinical data that we had and showed a very high potency that could functionally cure people of HIV.
Existing HIV medications, called antiretroviral therapies (ART), cause nausea, diarrhea, and fatigue every day, and lead to early aging, bone density issues, brittle bones, liver, kidney, and heart disease, or higher rates of cancer.
With AGT’s cell therapy treatment, patients will be able to throw away their anti-retroviral medication. They can never get AIDS or be contagious, and HIV would be out of their lives forever.
Is this how the COVID vaccine works?
COVID is an exceedingly thin slice of gene and cell therapy. Instead of viruses, they’re using what is called Lipid nanoparticles. It’s little droplets of fat that encapsulate messenger RNA, which looks like an instruction from the nucleus of your cell. When it gets into the cell, it will make exactly what is coded by the mRNA.
A vaccine is like getting the disease without getting sick. It simulates the signal of the disease that tells your body the disease is there, without all the painful and damaging effects of the actual virus. It makes your body react as if the virus was there, so you’re ready in case the real virus comes along.
In the case of mRNA, they were able to isolate the part of the virus that your immune system reacts to when it enters your body. They could sequence the virus, so they knew exactly what to look for, and they decided it was the spike protein, which is harmless.
Your muscle needs a lot of fat and energy to work, so when it meets the lipid nanoparticle that contains the mRNA that “codes” for the spike protein, it sees it as food. It melts away the lipid coat and the mRNA is released, instructing the muscle to make a spike protein. You end up with a big concentration of spike protein in your shoulder, which triggers your immune system to think it’s invaded by COVID. Your immune cells run to that area and create a whole immune response that can last for years. When the real virus comes along, it doesn’t stand a chance.
If you have an unprepared or weak immune system, the virus would come in and by the time your immune system detects it, you’ll already be sick. When you heal, your immune system will go back to what’s called memory level, and the next time the virus comes in, you can react pretty quickly and crush it. By taking a vaccine, you have prepared the immune system before the virus ever arrived, so you normally won’t even feel any symptoms when the “real” virus tries to get into your body. You’re also protected from the serious consequences of a “runaway” viral infection in your body (like lung or nerve damage, or even death).
What are some barriers to the standardization of gene and cell therapy, and how can they be overcome?
In an environment where things are getting better and cheaper every year, anything is possible. Gene and cell therapy are not standard of care now, but one day they will be because it’ll be cheaper than treating diseases in the old way. This is the nature of technology-driven industries. Gene and cell therapy have a lot of parallels to the microcomputer software industry in the way that it geometrically grows in power and efficiency.
Gene and cell therapy are like software for the human-computer, which is the human cell. The capabilities that we’re discovering in the software are quadrupling every year, and like computers, the cost is going down every year. It is that increase in power over time at decreasing costs that will lead to a beneficial revolution in medicine, where more and more of the world will be able to access cures to diseases that today are incurable or even untreatable.
If you look at gene and cell therapies that are available and approved today, there are miracle cures to things like blindness and crippling genetic defects, but they are also very expensive.
At first, it might not be available to everyone, maybe just people with really good insurance. Very few people could afford an IBM mainframe back in 1970, and yet we’re all using computers that are much more powerful than an IBM mainframe right now. They have reduced in size and cost so that even poorer nations are using them. We didn’t pay a million dollars for them, because that’s the nature of technology: it gets continually better and cheaper.
It took about 50 years for the IBM mainframe to get into our pockets. It will probably only take 30 years for everybody in first-world nations to be able to get whatever they want. It’ll probably only take another 10 or 20 years until anybody on earth can be cured of diseases because it’s cheaper to cure them than it is to treat them.
Moore’s Law said that the power of microchips that go into computers would double every year and a half in cost. Biotechnology has been following that track for many decades. The cost of sequencing the genome followed that line and then it dropped off like a rock. It was even faster than Moore’s law.
They call this industry biotech because there’s a technology associated with it, but this is the first time that a technology curve is an endemic driver of a new therapeutics technology. Tech has finally come to biotech.
That is the nature of technology. It just keeps on going because it gets refined. The initial discoveries are there, and the miracle of finding a vaccine for COVID and getting it out to the public within a year is no miracle at all. It’s just science.
The way that Moderna’s technology works, it should have taken them weeks to design the vaccine. The only reason it took a year is because of the required testing. But the reality is that you can make a vaccine for a virus within a month. Right now, that method is expensive, but it will get cheaper and more widely available over time.
How do you envision the future of biotech?
The more we know about genetics, the more we know about how our body works and the more accurately we can edit it. The more solutions we can create that leverage all that knowledge, the quicker we can move.
Eventually, we’ll know the exact effect of every gene, protein, and enzyme in your body. Over time, we’ll be able to simulate your entire body. The FDA won’t have to test drugs on thousands of people, they’ll just simulate the test on a computer and identify which hotspots require clinical testing because of inconclusive results, and which ones are 100% known.
Such simulations can be made against 3 billion sequenced genomes. In 20 years from now, computers will be able to do that in a day. Of course, researchers may still need to do some clinical testing, but only on very specific areas that were not provable in the existing data and simulations. If we only have to test a few small things instead of everything, we can shorten development time to nearly zero.
This may sound like a very optimistic view, but if I told you, back in the 1970s, that one day, computers would build everything for us, drive our cars, and fly our planes, you would probably have thought I was crazy. But, looking at the pattern, how could it not go there?
I started AGT 15 years ago with a vision for the future of biotech. We are one of the leaders in this industry because we have a perspective and a model that gives us more capabilities than other companies. We’ll continue to exercise that vision and try to cure as many things as we can, as fast as we can, to reduce suffering and death from serious human diseases.