Pioneering Treatment of HIV with Dr. Marcus Conant CMO of American Gene Technologies

Today on the show we welcome Dr. Marcus Conant, chief medical officer of American Gene Technologies. Dr. Conant was one of the first physicians to treat AIDS in San Francisco while running the inpatient dermatology service at the University of California San Francisco. Before anyone recognized the virus or understood that it was about to become a global epidemic, Dr. Conant took the lead in forming the Kaposi’s Sarcoma Research & Education Foundation in 1982, which later became the San Francisco AIDS Foundation. He’s dedicated much of his career to fighting for an end to HIV.

Full bio Marcus A. Conant, MD

Chief Medical Officer at American Gene Technologies

Marcus A. Conant, MD is a physician who treated thousands of HIV patients in the early 80s while running the inpatient dermatology service at the University of California San Francisco. Before anyone recognized the virus or understood that it was about to become a global epidemic, he took the lead in forming the Kaposi’s Sarcoma Research & Education Foundation in 1982, which later became the San Francisco AIDS Foundation. Marcus conducted early clinical trials, persevering despite seeing 94% of patients die during the epidemic’s first years. His clinical experience sensitized him to the suffering caused by the disease. As a physician with a holistic perspective, his work expanded beyond the strictly clinical, to include education, research, and advocacy. Marcus is currently a clinical professor emeritus at the University of California Medical Center in San Francisco. He has published more than 70 articles on the treatment of AIDS, testified in front of Congress multiple times, and is a powerful advocate for the LGBTQ community.

Links

Marcus Conant, MD, LinkedIn: https://www.linkedin.com/in/marcus-conant-056699229/

American Gene Technologies Website: https://www.americangene.com/

American Gene Technologies LinkedIn: https://www.linkedin.com/company/1127234/

American Gene Technologies Facebook: https://www.facebook.com/amerigene/

American Gene Technologies Twitter: https://twitter.com/americangene

American Gene Technologies Instagram: https://www.instagram.com/americangenetechnologies/

Qualio website:
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Transcript

Kelly Stanton: 0:17

hello everyone and welcome to From Lab to Launch by Qualio. I'm Kelly, your host, and we're glad you're tuning in today. Before we jump in, just a reminder to please rate the show and share it with any of your science nerd friends. We know you have some. Also check out the show notes if you have a story or a product you'd like to share with us. We love hearing from you. Today we're very excited to have Dr. Marcus Conan, chief Medical Officer at American Gene Technologies. American Gene Technologies is a pioneering biotech company headquartered in Rockville, Maryland. They're using gene therapy to cure human's most deadly disease. AGT is creating the foundation for a fundamentally new approach to medicine. Much like Apple's iOS platform for the iPhone. AGT is building a gene therapy platform so other scientists can build on its approach to develop new cures, much like software developers creating apps for the iPhone. This will significantly cut the time and cost of developing new drugs for a variety of diseases. We're really looking forward to chatting with Dr. Conant today about his experiences in the industry and journey to where he is now. So let's bring him in. Good morning, mark. Thanks for joining. Thank you Co. Um, to get us started, tell us about your background.

Marcus Conant: 1:30

Yes, I, uh, well, it's, it's a long and, and it's a long story, I trained, believe it or not, as a dermatologist, and was on the faculty at the University of California in San Francisco as a practicing dermatologist when the AIDS epidemic began in 1981. And the first cases that we saw were actually sarcoma, which is a skin disease. It's a multi, uh, focal, uh, malignancy appearing. It can occur internally, but it appears primarily on the skin. And so as a dermatologist at an academic center in San Francisco, which had a huge gay population, it was obvious that we would start seeing large numbers of those patients. So I started a clinic at the university. That clinic grew. Huge size. I started seeing patients in my private practice, ended up building the largest private aids practice in the country where we were caring for some 3000 HIV positive men. This was in the period when if you caught HIV, you had a 96% chance of dying, and so we lost a huge number of those patients. Um, but by 1996 we had highly active antiretroviral therapy and so suddenly it was like the Lazarus syndrome patients were coming back from the dead, uh, recovering their CD four counts were going back up and they were doing great. So I practiced dermatology. Yeah, it was Well, it was, it was a mi it was a miracle, you know, it re it was truly a miracle and it, it's sad that so much of that history has, has really been lost because we, we lost a whole generation of very bright young. Gay men who had moved to San Francisco or New York or other metropolitan areas to get away from the prejudice that they were experiencing in the towns where they grew up. And they were obviously bright, capable, able to get a job, find a boyfriend, settle down, and then suddenly at age 32 with a career ahead of them, everything working out, suddenly they're dying of a disease for which we not only had no cure, we didn't even know what caused. Let's think of how frightening that must have been when you know your doctors don't even know what you've got. But anyway, that was terrify the period. It was, it was terrifying. It was truly terrifying. And it was terrifying for us treating the patients because we knew we didn't know what we were doing, you know? But anyway, that was all in the 1980s. Now we're 42 years after that, and still, there are many things about the aids, epi, aids epidemic that we don't underst. We know now what causes the disease, but we, we, and we can suppress the, that virus with drugs, but we can't eliminate that virus from the body. And, and this will come up over and over in our discussion today, but one of the reasons we can't eliminate it is the virus literally becomes a gene. When you catch HIV, you're catching a. And it's integrating into your genome and it's there for the rest of your life. We can suppress it with drugs, but we can't go in there and take that gene out. And so that's now the challenge is how can we suppress that gene? How can we keep that gene from manifesting itself, uh, so that the patient gets a functional. And we can talk as we go later about other conditions where that seems to happen or doesn't seem to happen. It does happen, uh, in, in patients.

Kelly Stanton: 5:05

Absolutely. Well, it seems that's, um, one of the innate, uh, evolutionary Hmm. Amazing and horrible traits of viruses in general, right. We're, you know, you catch one, you've got it. Um, some just happen to be nastier than others, it sounds like.

Marcus Conant: 5:21

That's right. And, and we think that somewhere about 10% of your genome are viruses that our ancestors have caught in the past.

Kelly Stanton: 5:29

Interesting. Interesting. Well, I was gonna, uh, veer off in the direction of the Kaposi sarcoma. Research foundation, but I feel like we should keep on this viral thread a little bit. So, um, as far as the what AGT is doing and how the viruses and all of that sort of ties together, I assume that's still an area of active research and something you guys are trying to use to inform some of your tech decisions.

Marcus Conant: 5:54

Right. Well, yes, and let, lemme give you a little background. About 12 years ago, the founder of this company, uh, Jeff Calvin, uh, who came by the way from a computer background, he worked with Apple for, for many years. It suddenly occurred to him that, Hey, wait a minute, if many of these diseases are in fact genetic problems, perhaps we. Treat these diseases by either removing that gene or in some way blocking that gene so that the gene is no longer operational For, for example, CAPI sarcoma is caused by a herpes virus, which integrates into your cells. If your immune system's normal, your immune system suppresses capi sarcoma, you don't have it. But if you catch a virus like HIV, which destroys your immune system, the CAPI sar. Manifests itself so the virus is there and it only comes out when you're immunosuppressed. And so you take an AIDS patient who has CAPI sarcoma covering his entire body. You put him on highly active antiretroviral therapy. You suppress the HIV virus. His immune system RET returns. And what happens? The KS all goes away. And we saw that in hundreds of patients, it literally fades away in front of your eyes. And so what's happening there? The patient is still infected with H H V eight. He still has the ability to produce Capy sarcoma, but if you can someway suppress that gene, You can get a functional cure and think of it, many, many diseases are because you have either caught an inappropriate gene and it's manifesting itself, or you don't have a gene that you need. And if we could put that gene in the body, you've taken care of the the disease. And so that was what occurred to Jeff is, wait a minute, if we can now using some of the technology that we now. We can go, go into the body and either suppress genes or make or add genes that are there. We can get a functional cure for these diseases. And one of the first diseases to attack, of course, was HIV, it the, the disease is, as I said earlier, you are catching a gene. How can we suppress that gene? And so that's what we're doing. We're taking a lenti virus, and I'll explain it in a little more detail, but we're taking a lenti virus, we're putting, uh, constructs in there that suppress the HIV virus and, and then we're putting those cells back in the body and we're suppressing HIV so that it can't replicate.

Kelly Stanton: 8:24

Interesting. And if it's not actively replicating, perhaps it can't be spread.

Marcus Conant: 8:29

Correct. And we know that's from, from treatment with, with, uh, pharmaceutical medications, we know that's true. If you take pills and get your viral load below the level of detection for a period of six months, you are no longer infectious. You equals you, you are no longer infectious. And so if, if with our gene therapy we can suppress the virus down to very low levels, hopefully un to begin the patient undetectable. The patient will no longer transmit. and will of course not, not manifest in the complications of HIV infection.

Kelly Stanton: 9:04

Interesting. I'm not sure about, uh, what the side effect profile looks like of the, the retrovirals and the, those drugs that they have to take, but I would assume that in this genetic model, uh, you're dealing with less of those kinds of pharmacologic and side effect type activities. Right.

Marcus Conant: 9:20

And, and, and we have a little data of, not only from our studies but but from other studies as well. First about the pharmaceutical drugs, it is. Early on, the side effects were horrendous. I can remember starting the first patients on a c t, which was the first drug that we had that was affected, and that was in 1988, I believe it was. And that was an awful medication. You had to take it every four hours or so. You had to take it four or five times a day. You had to very large doses. Most patients that's upset, their stomach had caused all sorts of, uh, gastrointestinal complications. It made patients sicker than. But it did the important thing, it was proof of principle. It proved that there was a way to suppress the H hiv V virus with a drug. And so that starts the process. Aha. We know now that we can do it. Now let's find drugs that do it better and that have fewer side effects. And so that's what the American pharmaceutical industry did for, for the next 30 years, was they have now developed drugs that have hardly any side. It's only one pill once a day. It's usually a combination of two or three drugs in that combination. Cause this virus mutates very frequently and you can suppress the virus in patients that take the medication regularly in essentially all patients. And studies show that those patients live essentially a normal life. They can live as long as they would've lived had they not contracted. HIV the the problem. That they have to remember to take the drug every day. And that sounds really inter uh, easy. You think, well, you've got a fatal disease that can kill you. Any idiot can take the drug every day, but life gets in the way and so suddenly you don't have enough money to buy the drug this month. Are the car broke down and you can't get to the pharmacy? Are you happen to live in a rural area and you're too far away from the pharmacy? Are you a mother of three kids and you're h HIV positive and one of the kids is sick and you don't have time to get to the pharmacy? All of those problems come up, and so compliance is not a hundred percent. If you could put cells in the body, which will suppress the virus, and they're there for the patient's life, you no longer have any of those problem. And something else you accomplished. The patient that has to take a pill is reminded every day that he's HIV V positive. Yeah. Every day you go, you go there and you have to take that pill and yeah, I'm still HIV v positive. And all the things I wanted in life have been changed. I now have to see a doctor three or four times a year. I have to tell my sexual partner that I'm, say, HIV positive. Is there a chance that I'm, I could transmit this to someone that I'm intimate with? Oh, no, no, no. All of these questions, when I go to the pharmacy do they look at me different because I'm H HIV V positive. All the human concerns. If we could do it genetically, if we could take the patient's cells, modify them so that they can't get infected with HIV and put them back in the body, that patient then has a functional cure, which would suppress the virus for the rest of the patient's life. That

Kelly Stanton: 12:34

would be an incredible life change for them.

Marcus Conant: 12:36

That's right. And for all of us.

Kelly Stanton: 12:39

So where are, um, where is AGT in the process then of, of getting that developed?

Marcus Conant: 12:45

It's, it's always too slow. Kelly if it

Kelly Stanton: 12:48

never goes as fast, it's always too slow. I, I, I

Marcus Conant: 12:51

agree. Yep. Jeff, Jeff k has been working on this for about 12 years. I joined the company about a year and a half ago, and we've got some good data. We, we have put the, we, well, first, briefly, let me tell you how we would do it. You take the patient and you lecour, you take their own cells out. So just like you're taking blood for transfusions, you take the blood out, but you put the blood back in and you save the white blood cells. You take those white blood cells and you grow them up from hundreds into million billions, and you take a Len Virus vector, a Len virus looks very much like the H HIV virus, but you've rendered it so that it's no longer infectious. It can't spread from one cell to another, but it can infect those. And we have genetic conscripts in there that block DCR five, one of the, uh, uh, necessary, uh, molecules for the h HIV virus to enter a cell. So you block DCR five and you put that, uh, you take that antivirus vector, you put it into those cells, and so now those cells are protected against, uh, being infected with HIV. You infuse those cells back into the. And, and then hopefully the patient no longer can, those, those cells will no longer will kill HIV, but will no longer kill, be killed by the virus. We did seven patients in all of the seven patients. Three things. There were no adverse events. In other words, the patients didn't get seriously ill. The, the worst that we saw were what you see with a normal transfusion. People get headaches, people get chilled from a transfusion. That's all we saw. There were no serious adverse events that need to be reported to the I rrb. That's, that's, that's great. That's exactly right. That's, that's amazing. But but then, but then there are two other things that could happen. One is that the body could say, wait a minute, you've messed up my cells. That's no longer me. That looks different. Yeah. That's, that's non, non-self. And I'm gonna reject those cells. But that didn't happen. So we saw no rejection of the cell. But there's even something else sometimes when you do a, a, um, graph in Graftman, the graph rejects the host. You know, the cells could have said, you don't look like me. I'm gonna reject you. And that's called graft versus host disease. And that didn't. And so the things that we really wanted, was it safe? Yes. Looks like it. What? Did it reject the patient? No. Did the patient reject the cells? No. And the other thing we know is those cells persisted. Now, they didn't persist at the levels we want because they need antigenic stimulation. Those cells over time will slowly go away unless they're seeing virus. But these patients were still on their antiretroviral medication. And as I've told you, if you're taking your medication, you're not infectious. There's no ver very little virus in your bloodstream. And so those cells that we put in weren't seeing virus. And so over time we know that they decreased a number. Now when we took the patients off of their antiretroviral therapy, it looks as if those cells are active, but how active they are and how many we're still persisting, we don't know at this point. Gotcha.

Kelly Stanton: 16:11

Okay. Okay. Yeah, that's. What a fascinating trial to, to design Lots of, uh, lots of endpoints, lots of, lots of measurements along the way and,

Marcus Conant: 16:23

and lo and lots of unknowns. Yeah. Yeah, definitely. The things that you don't know is, for example, when you put the cells back in, how long do you wait before you take the patients off of their antiretroviral therapy? Do you do it right away? Do you wait a month? Maybe if you don't wait long enough, the cells don't engraft and they'll be reject. Well, you know, all these things we don't know. Okay. Of course, now as we do the studies, we will learn those things and so we're preparing right now to do another study beginning, hopefully next year, in which we will answer some of those questions.

Kelly Stanton: 16:55

Good deal. Good deal. And these are all inhuman or are you doing some in primate research or

Marcus Conant: 17:01

y Well, this is one, one of the bizarre things about HIV. The only animal you can infect. The human immunodeficiency virus is humans. It's humans. Yeah. Early in the epidemic, we tr Jay Levy, where I trained in San Francisco and others tried to infect other animals, you know, dogs, cats, rats, the things that you normally do. We were unsuccessful in infecting any other animal with HIV. And so the studies have to be done in humans. And of course, that re that requires. To be be subjects to volunteer for clinical trials, which requires a huge commitment, not only a commitment to engage in a trial where we clearly don't know all the answers, but the time that it's involved. For example, in the new trial, the patients will be seen probably once a week for some 30. Can you imagine the commitment of going in once a week to see a doctor and have blood drawn for a period of 30 weeks? That's a, yeah, that's huge commitment. That is a huge commitment yet. That That's right. And yet we found in this study there are people who care enough about this disease, who've seen enough people get sick from the disease, seen enough people impacted by HIV know the history of how many, we lost 800,000 Americans to this disease that we right now have 1 million, 200,000 infected Americans that we need to find an answer for this disease. And even if it's taken 42 years, the answer's. We, we know we can cure this disease. Because remember with Timothy Brown, the Berlin patient, he developed a form of cancer. The doctors caring for him said, look, when we, when we do a bone marrow transplant, let's don't just do a bone marrow to cure the cancer. Let's do a bone marrow transplant that has the CCR five mutation. Which is the very thing we're doing that will block HIV v replication and put those cells back in him. And they did that. And what do you tell they cured him? Yeah. And he lived another 10 years or so before his cancer returned and he and he died of his cancer. But during that period of time, they cured his HIV. And that's been done now in five other patients. So we know we can cure this disease. It's just how can we do it without having to do a bone marrow transplant?

Kelly Stanton: 19:29

Right. Right. Yeah. That's awfully invasive. Wow. Well, um, you're clearly passionate about this. Um, you're a physician with a very holistic perspective. What, what does that mean to you in, in this case? What does that mean to you in general?

Marcus Conant: 19:48

Well, you know, I, I was a dermatologist practicing at a university. I'd been practicing 15 years or so when HIV came along and suddenly I saw my neighbors, my friends, my colleagues, the people I went to the opera with dying of this disease. It's life changing because at first you think I'm just gonna be treating this people and it'll be over in a few weeks, and then it's a few months and now it's 42 years. And, and most of those people aren't there anymore. But I'm still here. And so as long as I'm here, I can continue this fight for them and for myself and for everyone else. Th we, we can cure this disease, but we've got to keep doing the work.

Kelly Stanton: 20:34

Definitely. Is there a, uh, particular, um, impactful story or interesting story along the way that, that you could share?

Marcus Conant: 20:44

Well, there are lots of them.

Kelly Stanton: 20:46

Lots of them I'm sure. Is there one that stands out? Maybe?

Marcus Conant: 20:50

Uh, well, one of them that I often tell is I had a very good friend, a gay guy who, um, I had known for maybe 10 years, and they brought, and this was before the first case was seen in 1981 of AIDS. They brought out my office. He had a splitting headache. And I couldn't diagnose him. He was obviously, he needed to be hospitalized. He didn't have insurance for PRI private insurance, but he was a veteran, and so we admitted him to the VA hospital that day. He went into coma that night and six months later he died. Okay. At autopsy, he had tuberculosis of the brain. Extremely rare. I mean, yeah, I've been, I've been in pr, I've been in practice now 60 years. I've never seen a case of tuberculosis of the brain.

Kelly Stanton: 21:44

I didn't No, you could get it in the brain.

Marcus Conant: 21:46

Well, well, you, you see what it is, is a very rare opportunistic infection. Hmm. His boyfriend at the time was an IV drug user from New York. Okay. And this was four years before the AIDS epidemic. In retrospect, he had aids. We didn't know it at the time. What we would, what I'm trying to point out is we were seeing the disease, but we were not recognizing what we were seeing years and years before the epidemic really began, and in all probability, he contracted the disease from his IV drug. Using boyfriend was immunosuppressed. The tuberculosis manifested itself in his brain and killed him. Unfortu. So, so those kinds of things, you know, throughout the, the epidemic, one really strange event after another that is

Kelly Stanton: 22:43

the Wow. Yeah, I, I, sorry, my brain is spinning a little bit with how do you connect, how do you even begin to connect those dots? Um, but definitely I think in retrospect now, seeing, you know, and I think probably today, uh, although I would say certainly, you know, COVID is nowhere near, um, Uh, the, the impact seems to be a more of a flash in the pan compared to, to something like HIV. But yeah, there's, I think probably for our general listeners, just thinking about some of those parallels with seeing some different kinds of infections or different presentations and, and then realizing later that you've connected all those dots together. Yeah, that's, uh, yeah,

Marcus Conant: 23:26

but, and, and then to your point, it, it, it makes two points that, that I think are important. One, it points out, and Covid made the point very clearly that if we had better surveillance so that we recognized infectious diseases as they appeared. Yes. If we had a worldwide system of recognizing diseases like Covid or like AIDS early on, we could hopefully prevent the 10 million people that have died worldwide from. Right. But the other point that I keep trying to make is, remember HIV for the first 10 years of disease killed 96% of the people that got the disease. Yeah. If, if, if, if a young man came to me and, and I told him that he was infected with HIV, what I was telling him is, you're going to die. And no one wants to hear that. Okay. Right, right. Covid only kills by about 2% of the people that. Okay. What if it, what if Covid had killed 20% of the people that got society would've collapsed? Yeah.

Kelly Stanton: 24:33

That's a very different

Marcus Conant: 24:35

scenario. It's a, it's a huge difference. Right? And, and are we really prepared for that to happen? And then you say, well, it's never gonna happen again. The, the Spanish flu epidemic was exactly a hundred years ago in, in, in, uh, 1918. And, and, you know, and here, this, and this disease, of course, has killed more people, but there are more people living today than there were then. But, you know, the same thing happened a hundred years ago. But in the interim, we've had Zika, we've had Ebola, y you know, the list. We've had aids, the list goes on and on and on. And the chances are we will have another major. which not only will shut down society like we've seen, but may in fact kill more people than Covid and will totally disrupt our ability to function as a society.

Kelly Stanton: 25:22

Yeah, definitely. Definitely. Ugh, goodness. Well, if you could go back and tell yourself something at the start of your career, what would it.

Marcus Conant: 25:34

Oh, well, I've found out that a lot Cause you know, when, when you get to be an old man, you start thinking about what would I have done differently? You know, in, in my life, looking back, I probably would've become a virologist rather than a practicing physician. I mean, I find that incredibly exciting. But, but who knows? You know, I, I've been truly. Being on the frontline of lots of things on the frontline of HIV happening in San Francisco 42 years ago now, on the front line of gene therapy and a way to try to cure this disease. So I really can't complain about how life should be different because it's, it's been pretty good.

Kelly Stanton: 26:11

Definitely. Well, and, and some might argue that your, um, your broader focus, uh, in medicine perhaps brings a different perspective than specializing just in virology, for example. Perhaps, perhaps Um, awesome. Well, last question. My fun question of the day, I always like to ask, um, if I walked into a bookstore like Barnes and Noble, where would I find you? What

Marcus Conant: 26:41

section? Oh, that's a good que That's a very good question. Pro probably. I mean, if you ask me what I'm reading right now, uh, I'm reading Bruno, she's dome about the guy who built the dome over the cathedral in Florence. So outside of medicine, my, my interests te tend to be historical.

Kelly Stanton: 27:06

Historical. Interesting. Well, and they, they do play together so nicely. There's so much, um, medicine involved in, in all of history.

Marcus Conant: 27:15

That's exactly right. And so much history of.

Kelly Stanton: 27:18

Definitely. Well, thank you so much for your time today. I really appreciate it. This has been interesting discussion. Uh, where can folks go to connect with you or follow along, um, with the therapies

Marcus Conant: 27:31

American Gene Therapy. Um, they're, they're on the web, uh, with a huge presence. If you, if you, uh, just go to your computer check for American Gene Therapy, you'll. Awesome.

Kelly Stanton: 27:45

Thank you so much for your time. Have a wonderful rest of your day. Mark. Thanks Kelly.