Welcome to the EmpoweredPatientPodcast.com show. I'm Karen Jagoda, and my guest today is Dr. Adam Kaplin. He's the Chief Scientific Officer of MyMD Pharmaceuticals, mymd.com. And the topic today is extending the healthy human lifespan.
Thanks so much, Karen. Glad to be here and glad to be able to talk about what I hope are exciting topics in drug development related to aging.
Let's just start by talking a little bit about what the mission of MyMD is, particularly as it's related to extending the healthy human lifespan.
Sure. So, essentially what we have is a drug that gets to the cause of inflammation as one of its primary mechanisms of action. And since inflammation is involved in so many aspects of health and disease, health being fighting off infections, but disease sometimes getting confused and fighting off the body, which results in an autoimmune disease, like multiple sclerosis or thyroiditis, autoimmune thyroiditis, both of which this drug has been shown in preclinical studies to help.
But also, inflammation is involved in aging as well. So, probably one of the core features of pathological aging is chronic inflammation, that combined with some additional factors that I don't know if we're going to get into today. But for us, the exciting part is that we are going at the ability of this drug. Which is hopefully going to be coming out in a matter of months, a publication out of Hopkins that shows it delays aging in normal mice.
By delaying aging, what I mean is they not only lived longer, but they didn't lose their function. So, they retained their strength and their cognition. Because if we were only developing a drug that would just allow us all to get older and demented, that wouldn't be good for the economy, good for our personal health, good for anybody. So really, what we're excited about is the prospect of actually slowing the aging process and extending the healthy portion of our lifespans.
And the idea here is to not just treat age-related diseases but to delay the onset of those diseases. Is that right?
Yes so that's a really good way of putting it, Karen. Essentially what many people don't appreciate is that none of us are getting out of this life alive, so to speak, and what really gets us, in the end, is aging. So what I mean by that is if you completely eradicated all cancers, just gone, you have a fairy godmother who waves a magic wand, and all cancer is gone from human existence, you would extend the human lifespan by two, maybe three years.
Extending the Healthy Human Lifespan
by Addressing the Cause of Inflammation
with Dr. Adam Kaplin MyMD Pharmaceuticals
An Empowered Patient Podcast Published April 5, 2022
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And then you say, "Well, gee, that's a small percentage. How come only that amount?" Well, the reason why is if you sort of look at a graph, that with time the risk of getting cancer goes up, but right behind it is the risk of getting some pulmonary disease. Some lung disease, some heart disease, some brain disease. And if one falls, then the other one is right behind it. So, really what gets us is the aging process.
So the idea is if you want to make some major breakthroughs in extending people's function and quality of life and longevity, you really have to go after aging. Because any one of these other diseases is only going to clear the way for the next one in line.
And the idea here is that aging is somehow related to inflammation. And so tell us a bit about what your lead clinical compound, MYMD-1, is doing and what it is affecting?
Sure. Great question. So, aging probably is going to end up being the result of two primary processes. One is inflammation, and that is the product of having an immune system which is all set up to fight off infection. And not just fight off infection -- it turns out, inflammation is also a part of how we develop. So having the ability to get rid of neurons that are not connected ... we're born with way more neurons than we possibly need. And the ones that don't connect, you want to get rid of. Because you don't want them cluttering things up.
That also is done by the cleanup crews in the brain, which turns out to be the immune system of the brain, microglia. Inflammation is one of the core parts of development but also aging. If the inflammation is chronic and goes up over time, it can lead to accelerated aging.
Then the other part is that we burn fuel. All of our cells, in order to have the energy to do the things they do, need to burn fuel. And that's mostly glucose. And then, for storage reasons, fats. In burning fuel, we make some byproducts that are not so good. These byproducts can be injurious to cells. They're often called free radicals, and they cause free radical damage or oxidative injury to cells from these byproducts. So, this free radical combined with inflammation is probably the cornerstone of this aging process.
Now the drug that we have is unique in several factors. The easiest to understand, I think, the one we have the most data on, is the fact that it is a TNF-a inhibitor. TNF-a is tumor necrosis factor alpha. It is a cytokine, meaning it is what communicates between two immune cells. Just like two neurons have neurotransmitters, immune cells have the cytokines to communicate.
Extending the Healthy Human Lifespan
by Addressing the Cause of Inflammation
with Dr. Adam Kaplin MyMD Pharmaceuticals
An Empowered Patient Podcast Published April 5, 2022
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But TNF-a turns out to be the master regulator of the immune system. It's the first one to go up if you get infected with any bacteria, fungus, or virus. And it also is up chronically in a number of autoimmune diseases. In fact, so much so that the number one grossing drug in the world is HUMIRA which is a drug that inactivates TNF-a. So we think that ours has certain advantages over the existing TNF-a inhibitors. Can I tell you what those are?
Yes. Please.
First of all, MYMD-1, our lead drug, can cross the blood-brain barrier. And that's a big deal because all of the existing TNF-a inhibitors are large molecules, large building blocks of immune globulins -- antibodies essentially -- or strung together series of receptors to TNF-a. So they just go out there, and they soak up TNF-a. They're like a specifically targeted sponge that just grabs TNF-a wherever it sees it.
But these large molecules can't get into the brain. Why is that a big deal? Well, it turns out that these molecules can have really toxic effects sometimes. For instance, we know that there is an MS-like condition that can be created by being on these drugs. And I've actually seen this in the clinic. Which is if you get put on this type of drug, not commonly, but certainly occasionally, it can have toxic effects. Those cells, when they cross over into the brain, see this very high level of TNF-a, and they sometimes get overactivated. Then they can lead the inflammation and damage in the CNS. We don't have that with MYMD-1.
The second most important thing I think is that these drugs, the anti-TNF-a treatments like HUMIRA, do not have any benefit for the brain. I mean, they can cause things that look like MS, but they certainly have no benefit for CNS inflammatory conditions. And among those are MS, lupus, but also dementias. Alzheimer's now has been implicated to have inflammation involved. So, crossing over the blood-brain barrier's a big deal. It's orally available. Additionally, all the other TNF-a inhibitors have to be taken by a needle in some way, injection or infusion.
And they're selective. So what is really interesting about the selectivity of our MYMD-1 drug is that TNF-a, as I say, is the first harbinger, first mobilizer of the immune system. If you get an infection for any reason, something crosses your gut or into your blood and crosses the blood barrier. So you want TNF-a around when it's produced in the blood by what are called monocytes or macrophages. You don't want it overexpressing itself when involved in autoimmune disease like B and T lymphocytes.
Extending the Healthy Human Lifespan
by Addressing the Cause of Inflammation
with Dr. Adam Kaplin MyMD Pharmaceuticals
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Well, it turns out, our drug only inhibits the production of TNF-a in B and T cells, not in macrophages. And that's, again, a big deal. Because a lot of the bad things that can happen from the anti-TNF antibody treatment that currently exists are that they can cause severe infection, like pneumonia, and up to and including death and there is a black box warning on these drugs. The fact that we don't inhibit the macrophages suggests that we won't have that problem.
What did you learn from COVID-19 when it comes to cytokine storms?
Yes. So again, great question. The first thing I think that we've all learned is that thank God this only happens once every hundred years, God willing. But what we've all learned is that this inflammation is what really is the problem. It's not the virus itself that causes and unleashes this incredibly toxic effect on the lungs. It's what happens when it leads to overactivation of the immune system, and it's the immune system that really melts the lungs in really awful cases of COVID-19.
And this inflammation is known to show up, as you say, as a cytokine storm. This is because the immune system just gets way too activated and overexcited when it sees this virus, and it's trying to fight it off. There's all of this kind of bystander injury. Imagine that if you're in a war and you have these big bombs, and you set them off, and they're going to blow up not just the target but the surrounding targets. And that's what happens here with COVID-19 and inflammation.
And one of the things that we know is it does affect the brain. For instance, we know that three months after COVID infection, 50% of people will have clinical depression. A significant proportion of that group will also have cognitive impairment, this fuzziness that is often part of long hauler syndrome, which has been characterized in about 10% of patients --but probably is present in a higher percentage of patients.
So being able to call off this chronic immune process is critical in being able to weather storms like COVID-19, which is more of an acute leading to a chronic condition. It's an accelerated vision of what we've been going after to try to calm down autoimmune diseases and delay the inflammation in the tissue with pathological agers.
Where are you in clinical trials with MYMD-1?
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by Addressing the Cause of Inflammation
with Dr. Adam Kaplin MyMD Pharmaceuticals
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Yes, so we've been fortunate enough to get through the phase I study, which means we've used MYMD-1 in healthy volunteers, and it had no major side effects. So, although, again, there is a relatively small number of people that you use in phase I studies, there were no side effects really of any significance. And what we ended up then being able to do is get the FDA permission to do an investigational new drug trial, examination for sarcopenia.
Sarcopenia is muscle wasting. So what happens to people with excessive sarcopenia is they have lots and lots more chances to fall and break a hip and the like. It's been shown by, in fact, a world-class group of researchers, led by Jeremy Walston at Johns Hopkins, that the level of inflammation, specifically elevated TNF-a receptor 1, one of the receptors for TNF-a, is a hallmark of sarcopenia. A very good readout, biomarker if you will, of pathological aging.
So, we are taking patients who have elevated levels of TNF and TNF-a receptor I. And we are then seeing the ability of MYMD-1 to slow that process down and decrease the inflammation. Then eventually, look at its effect on muscle wasting, and see if we can preserve muscle function and strength in patients who are at risk of losing that as they age.
Do you see MYMD-1 being used in conjunction with other drugs that are out there to address very specific elements of the aging process?
So right now, certainly, if you're talking about drugs that have had trials going on and in mammals. The drug that has perhaps the best data is rapamycin, which is an anti-inflammatory molecule used to prevent kidney and organ rejection after transplant for instance. Another drug is also resveratrol, which is the substance that got a lot of publicity as being in red wine. And again, these are drugs that have been studied to delay aging.
What I can tell you is from the study done at Hopkins, although these results are not even published. But I can just perhaps pique your interest and let you know the preliminary results. Compared to rapamycin, MYMD-1 was four times better at preventing the aging process. And resveratrol has an even smaller effect than rapamycin.
So there have been other ways, dietary ways of prolonging life. But of course, medications, but there really aren't many out there that have shown any significant benefit in mammals. And so we are, to our knowledge, one of the first, if not the only FDA approved, double-blind study of aging-related processes that are into testing in mankind.
Extending the Healthy Human Lifespan
by Addressing the Cause of Inflammation
with Dr. Adam Kaplin MyMD Pharmaceuticals
An Empowered Patient Podcast Published April 5, 2022
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What I mean is that the FDA doesn't look at aging as a disease. Because it's understandable from their standpoint, aging is a part of the life process. As they say, none of us are getting out of this life alive. What they do allow is not for aging, but they allow us to look at pathological processes as our target, like sarcopenias which is a form of advanced pathological aging. Really, this is the best that we can do, given that there are no drugs out there that have been approved to delay aging.
Thanks to my guest today, Dr. Adam Kaplin, Chief Scientific Officer at MyMD Pharmaceuticals, mymd.com. Follow them on Twitter @MyMDPharma. I'm Karen Jagoda, and you've been listening to the EmpoweredPatientPodcast.com show. Follow me on Twitter @KarenJagoda. Like us on Facebook at Empowered Patient Radio. Thanks for listening, and we'll see you next time.
Extending the Healthy Human Lifespan
by Addressing the Cause of Inflammation
with Dr. Adam Kaplin MyMD Pharmaceuticals
An Empowered Patient Podcast Published April 5, 2022
