Scott Neidhold 00:09
Hello and welcome to Pathfinders in Biopharma, the podcast series from RBC Capital Markets, where we uncover the key trends and catalysts shaping the fast moving world of biotech and pharma. I'm your host today, Scott Neidhold, Director in RBC’s Life Sciences Investment Banking Practice. In this episode, I'll be talking with special guest, Kristin Fortney, CEO and co-founder of BioAge, a company that harnesses the biology of human aging to develop new therapies for metabolic diseases. She will be unpacking the nuances of longevity and the biology of aging, the interventions that can address the challenges of age related diseases, and current and future opportunities for biotech investors.
Scott Neidhold 00:58
So Kristen, it's great to have you on the podcast.
Kristen Fortney 01:00
Yeah, thanks for having me.
Scott Neidhold 01:01
I want to start at the beginning. You're a scientist by training. Your background is in aging biology, genetics and bioinformatics. You founded BioAge in 2015. Can you tell us a little bit about your background and what inspired you to go on this journey to understand and address aging, and ultimately found BioAge?
Kristen Fortney 01:21
Sure happy to start at the beginning. So as you mentioned, my research career, my scientific training, was really also in aging biology, really more from a computational, statistical perspective. And I was really excited about this area of science, because it seems like it could have really profound consequences for human health. There are now a growing list of interventions, drugs or therapies you can give to a mouse, for example, right, that let the animal live healthier longer, that delay the incidence of multiple different diseases. And if those could be translated to a human context, that would be really exciting for the health of the entire population. And as you mentioned, most recently, before founding BioAge, I worked on the genetics of exceptional human longevity, in particular, that was at Stanford. And what's exciting there too is just, just how concrete it is, right? There already are a lot of people who live to be past the age of 100 or even 110 and are still physically intact, cognitively intact. And we really want to learn from those examples, and that it was really those ideas that led to the founding of BioAge with my co-founder, Eric Morgan, and we really wanted to start out from the outset by studying long lived human populations, people who are already aging successfully, seeing what was different about them, and then using that knowledge and those discoveries to help inform drug discovery for the rest of us.
Scott Neidhold 02:39
When we talk about the biology of aging, are we talking about lifespan, health span, both? And what does that distinction mean in the context of this work?
Kristen Fortney 02:47
Yeah, I think that's a great question, right? Like when you're when you're talking about extending lifespan, extending animal lifespan or human lifespan, what does that actually amount to. Like, none of us want to be sick for an additional 10 years, right? So there are these two very different concepts of lifespan and healthspan. Lifespan is how long you live. Healthspan is how long you're healthy. And what we ultimately care about is having all of us be healthier longer, right? Like delaying the incidence of age related disease, ‘compressing morbidity’ is one of the phrases that we use in the field. So if you look at these, these humans, as I mentioned, who live to be over the age of 100, what's interesting is that you find they're not sicker for longer. They actually tend to get sick at an older age and spend a smaller proportion of their life being sick. So that's really what we're aiming for here, extending the healthspan.
Scott Neidhold 03:37
So you said something really interesting there about compressing morbidity, and I want to dig into that a little. One of the hallmarks of developing drugs that target aging biology seems to be early intervention, and the way that identifying and intervening early in long-term pathologic states is a critical vector to avoid or delay disease before it starts. Chronic inflammatory states is an interesting example. So maybe using that as a model, you could talk a bit about the early intervention framework and the benefits of targeting disease drivers before they advance.
Kristen Fortney 04:12
An important point here right, is that this is really concrete science that will have applications to very specific diseases, aging is the biggest risk factor for so many different diseases, from Alzheimer's to heart disease, it’s a very long list. And what we're learning more and more in disease biology is that we have better outcomes when we intervene earlier, right? And you know, when you're when you're older, when you're 60s, 70s, 80s, you can still be healthy, but at the same time, you are more likely to develop a disease. That disease is more likely to be serious when you do get it, right? So what is it about the age state that predisposes you to disease? What can we learn about the biology of disease by looking at it through that window? So just to take a very concrete example, one pathway, an inflammatory pathway, that we're really excited about at BioAge, is NLRP3 the inflammasome. Inflammation goes up as you get older, you get more and more inflammation – that predisposes you to a whole host of different diseases. And there may be some targets that you know, like NLRP3 inhibitors which can be effective not only in treating those diseases first, but potentially in intervening as well earlier in the courses of those diseases.
Kristen Fortney 05:18
So, as I mentioned at BioAge, we've developed brain penetrant NLRP3 inhibitors that we're really excited about, that will be going into the clinic later this year, about multiple applications of metabolic disease, but also, more broadly.
Scott Neidhold 05:30
Let me ask a follow up question on the NLRP3, what's the connection between neuro inflammation and obesity?
Kristen Fortney 05:38
In the obese state, there is additional inflammation, and especially neuro inflammation, and there's very nice evidence in animals that by tamping that down, you can help correct appetite and improve obesity and correct it.
Scott Neidhold 05:51
So the conventional wisdom is that there's sort of a big three for long-term health, diet, exercise and sleep. And genetic differences may calibrate the relative impact of those from person to person, but I think in general, we can all benefit from eating better, exercising more and getting adequate sleep more consistently. I think diet and the downstream consequences has gotten a lot of attention and focus, but you all are doing some work around the second one, exercise. Can you talk a little bit about that work and what we might be able to learn from the biology of exercise.
Kristen Fortney 06:27
We're very excited about the biology of exercise. If you think about it, this is potentially only the really proven anti-aging intervention. This is really very promising biology to be able to mimic with a therapeutic. And what's interesting, too, of course, is the intersection of that with aging. A lot of your body's key responses to exercise decline with age. And that's really problematic as you get older. Actually, one of the targets we're working on at the company, Apelin, is exactly this kind of target. So Apelin is a circulating factor in your blood that declines with age. And Apelin is also something that your body makes a lot more of in response to exercise. It's called an exerkine, and we believe that Aplin mimetics will have multiple metabolic benefits. And more broadly, on this same concept, we announced at the company in December that we're going to be partnering with Novartis to discover new targets at the intersection of aging biology and exercise. And if you think about it, we're kind of studying two different kinds of biologies that, in some sense, work already, right? We're really studying very large human populations with bio banks, and looking at what's different at the molecular level, between people who are very functional, physically and mentally, when they're old, versus people who are not. We're really characterizing that with modern proteomics, metabolomics, etc. So we're trying to say, ‘Hey, what already works for these people to age better? What were those molecular differences?’ And what we're doing with Novartis is we're really comparing that with the response to exercise. The benefits of exercise are really mediated by your biology. There are factors that go up, that go down, that help translate these benefits into benefits for your body. And if we can understand what those switches are, other potential targets, like Apelin, like FGF 21 for example – that's also an exerkine – that could be a very rich source of new drugs that are relevant across multiple different conditions, from metabolic to neurological.
Scott Neidhold 08:16
So you mentioned your partnership with Novartis, and I want to ask you about the role of large pharmaceutical companies in this field. Clearly, they're going to have a big role to play. How are they engaging with the space today, and how do you think that will evolve going forward?
Kristen Fortney 08:31
So, you know, as we've touched on, aging is really still very much a new science. So I think it's great that we're seeing pharma come out and explicitly work more on aging biology – like Novartis, as we mentioned, they actually have a new division dare diseases of aging and Regenerative Medicine, which is, this is part of the one of the biologies that they're really deeply exploring, and that's new, right? So I think there's this growing recognition that we can discover important new targets for disease by looking at the biology of aging, by looking earlier in the course of disease, which is really looking at the changes that happen as you age.
Scott Neidhold 09:05
It's easy to imagine the search for therapies effective against aging as this sort of quest for the Holy Grail, as though there's some magical discovery that we're going to come upon, and it's going to stop time. But aging is really complex. I think it's likely to require a multi-pronged approach. Is that the right way to think about it? Is there a Holy Grail out there waiting to be discovered? Or is it more about expanding the toolkit with effective targets, some of which you mentioned, FGF21, might be sort of hidden in plain sight, sitting in people's pipelines today?
Kristen Fortney 09:41
Yeah, some great questions there. So first, I mean, I don't think there's any Holy Grail, right. Aging is kind of, it predisposes you to many different very complex diseases, each of which of those has many relevant targets. So aging itself is going to be complicated. At the same time, I do think there are going to be individual targets which could have substantial effects, right? I mean, look at anchor 10s, look at FDF21 right? There are large patient populations where a single target, a single drug, can have a very meaningful impact. And I think that will be true in aging as well, though, of course, potentially in the future, to get the best possible outcomes, we might have to go multi-mechanism. As we look to expand the universe of different aging targets, I think there are a couple of very notable examples of classic aging targets which have been very successful in the clinic, which is really, really interesting, even though they're not necessarily thought of first as aging biology targets. FGF21 is probably one of the best known aging targets. If you look across all the literature on aging biology, at all the different things that people have tried to do to a mouse to make it live longer. It's a very short list of interventions that will reproducibly make black 6 mice live longer, because it's very hard thing to do, and you have to get everything right. And if you increase FGF 21 in a transgenic animal, they live about 30% longer. It's a really interesting finding. And so, you know, with the Quiroz work, we're seeing that that same target translate very nicely into human populations in metabolic contexts. There could be other benefits as well, there were in the animals. So I think that has to be more fully explored. And to take another of my favorite examples, New Amsterdam pharma works on CTP inhibitors, and this is actually a gene that, where they've observed mutations in human centenarians. So some humans who live past the age of 100 have mutations in this gene that are, you know, not too different from what the drug is doing. So it's been a target of interest in aging biology for some time. So I think that there's a lot of promise in looking at this biology.
And at the same time, I really do think there's a lot of undiscovered biology of aging. It's really been an under resourced scientific field for a long time. One of the very exciting findings was that IL-11, interleukin 11, if you knock it out, that can make a mouse live longer. And that, you know, was a surprising finding to many. It's going to yield a lot of interesting new work in biology over the coming years. And I think there will be other targets like that where we just haven't looked.
Scott Neidhold 12:02
So, it feels like aging is having a moment right now. It really kind of feels like aging, longevity, life extension have kind of captured the zeitgeist, at least respect to the intersection of science and sort of mainstream or pop culture. And it's not just the press, it's company formation by folks who aren't necessarily from the industry. It's different kinds of investors popping up and looking for ways to get involved. My question to you is about whether you're feeling that from where you sit, you know, is there a heightened interest in your work that you're feeling? Where is that interest coming from, and what do you think it could mean for the future of the field?
Kristen Fortney 12:39
Yeah, I think there is a heightened interest in the field. I think it is part of a broader trend. People are realizing the potential. Partly too, you know, I think an important example is the anchor tents, right? It wasn't that long ago that people thought obesity would be a very challenging indication, which is ultimately what it's about, that's what reimbursement is about. Now these are the world's most valuable drugs, where they have the potential to expand indications. You're seeing people pay out of pocket, which maybe makes you think differently about what types of medicines people would pay for. And some of that is going to be relevant, like, what if you had a drug? We don't have a regulatory path for this yet, but what if you had a drug, which could slow down your loss of muscle and reduce your risk of frailty as you age? Would you pay for that? So I think that it's, there have been some recent developments in biotech as well, right, which are really driving the interest and the trends here.
Scott Neidhold 13:29
You mentioned regulatory, and I wanted to ask you about that. Is there anything unique, or maybe uniquely challenging to developing therapies for age related disease or longevity? You know, what's the current framework? Is it evolving? Does it need to evolve? Or is it just sort of, you know, business as usual, in terms of from a drug developer standpoint?
Kristen Fortney 13:51
Yeah, that's a great question, and it's hard to give a blanket answer. In many cases, it is business as usual, right? So, I mentioned that we're developing NLRP3 inhibitors. These could potentially be used very early in the course of disease or aging one day if there's, of course, no regulatory path for that, I can't even imagine what that trial would look like. Probably not feasible, but they are also, can be used to treat specific diseases. So there's a very clear regulatory path, there's a very clear commercial path. There are ways to expand the treatable population over time, as we've seen with other therapies and other indications. So, it's really just business as usual in that case, right? There are multi-indication drugs that are not aging drugs too. There's nothing that's very exotic about that. At the same time, though, I think there are some mechanisms of aging where there isn't a regulatory path today, where there could be, and where that could really be beneficial for the population. And one example that I really like to highlight there, is sarcopenia. As you become frail, as you become sarcopenic, you lose you lose independence, and that means you have to go into a nursing home, which is a terrible outcome. This is something that is measurable, right? There's there are end points that you could use. If there were a regulatory path for sarcopenia, I think there are a lot of medications there that could help a very large segment of the population. And that's, in some sense, a more classic aging indication, like, is it really a disease? We don't really consider it to be such today, but it definitely has its very severe impact on quality of life. I think there are some sort of branches of aging biology where there's that hurdle today, and if we had a path forward for sarcopenia, for frailty, that could really accelerate innovation there. We're seeing, for example, I think, more interest on the part of the EMA or in Japan, because of their aging populations, this is having a real consequence on their economy and on the health of the population, and I’d like to see that kind of innovation here in the US as well.
Scott Neidhold 15:38
So you mentioned a regulatory path for sarcopenia being a big unlock. And I wanted to ask a question in this vein, is there something that we're sort of waiting on? It could be regulatory, scientific, societal, that really advances us into the next phase of this field? And a related but separate question, when you think 5, 10, 25 years out, what does success look like? Where do you hope we are, and what will it have taken for us to get there?
Kristen Fortney 16:08
Yeah, that's a great question. And of course, it's always multifactorial, right? I think two components that we need to unlock an indication are, one, a drug that works, it has a profound effect, and two, sort of, really like alignment on an endpoint that didn't exist before. And again, you can go and look at obesity, right? The incretins, they work. They're very effective. At the same time, people were working on incretins for a very long time. This, this whole revolution could have happened earlier, right? So, it's a combination of biology and a combination of, you know, what are the endpoints that we can, you know, get around the table and approve and move it, move in a very effective way. And part of, part of the challenge, I think, with sarcopenia, is that the classic endpoints that you might look at for function, they're so noisy, like, incredibly noisy. There's so much variability. So I think that, you know, there's a few different things that could come together to really transform that. And where I'd like us to be, you know, in a couple of decades, is to have drugs approved for frailty, right? That could really make a huge impact.
Scott Neidhold 17:05
So let's, let's range back to today. When you look around today, what gets you excited? What are some emerging discoveries or breakthroughs that you kind of, you know, do a double take and think are really important that maybe aren't on people's radars.
Kristen Fortney 17:18
So what most excites me is that, like, there's a clinical pipeline today where there wasn't before. So there are a number of mechanisms which are classic aging mechanisms, like NLRP3, FGF21, etc., that could really have an outsized impact on health. So that's exciting, right? I think there are a lot of exciting discoveries just in the past few years. Like what I mentioned earlier, there's an exciting new target, IL-11, which seems to have broad protective effects on longevity. There's the whole discipline, for example, of epigenetic reprogramming, right? This concept, this still sort of early science concept, that you can reset some of your cells to a younger state that can have broad benefits for the organism. And that foundational science led to the formation of a bunch of exciting new companies working on that as well. There's even technology breakthroughs as well, right? So better ways of quantifying biomarkers, both with, you know, wearables, but also with, you know, proteins or methylation sites, can lead us to more accurate, accurate, accurately measure aging in the clinic as well.
Scott Neidhold 18:15
It's exciting stuff. You know, there aren't many things that you can say have 100% prevalence. I think maybe the only one. So I'm sure we're all rooting for you and for BioAge and for all the folks who are working to advance this field. Kristen, thank you so much for taking the time with us today. It's really been a pleasure and super interesting to hear about your background, your work.
Kristen Fortney 18:40
Thank you, Scott.
Scott Neidhold 18:47
Thank you for listening to Pathfinders in Biopharma, a podcast series from RBC Capital Markets. This episode was recorded on April 23, 2025. Listen and subscribe to Pathfinders in Biopharma on Apple podcasts, Spotify, or wherever you listen to your podcast. If you enjoyed this episode, please leave us a review and share the podcast with others. Thank you.