BioAge CEO talks NLRP3 and ‘pipeline in a pill’ ambitions

Introduction to BioAge

0:00Today is Friday, May 22nd, and you're listening to The Top Line, brought to you by Fierce Pharma and Fierce Biotech. I'm your host, Ayla Ellison. There's a certain kind of biotech story that sounds almost impossible at first.

0:30A company spends years studying human aging data, looking for clues in people tracked over decades, and then tries to turn that biology into medicines. That idea used to sit closer to the edge of the industry, somewhere between ambitious and speculative. But lately, the conversation has started to shift. Inflammation biology is gaining new momentum. Obesity drugs are changing how people think about prevention.

1:01And longevity science is moving closer to mainstream drug development. This conversation was recorded last week at Fierce Biotech Week in Boston, where I sat down with Kristen Fortney, the co-founder and CEO of BioAge. We talk about the decade-long bet behind the company, why BioAge is focused on aging biology as a way into metabolic disease, and how its oral NLRP3 inhibitor could become what the company

1:34calls a pipeline in a pill. Let's get into it.

1:49Kristen, thank you so much for joining this episode of The Top Line today. I wanted to start by taking a little bit of a look back. So you co-founded BioAge. It's now been over a decade ago around a pretty specific intellectual bet that if you studied people who were aging unusually well, you could find drug targets that everyone else was missing. At that time, that wasn't an obvious way to build a biotech company.

Founding BioAge

2:17So could you walk us through what made you confident enough at that time in that idea to build a company around it? So my background as a scientist is really in the biology of aging, the biology of human aging. And what I found really exciting about that science was that there seemed to be some biology that underlied multiple diseases at once. Right. Like there were there are interventions, there are genetic interventions, there are medicines you can give mice that make them live longer. And in order to make them live longer, you have to really delay the incidence of multiple age related diseases.

2:49And so that was always really exciting. Like, what are these targets from aging biology? Wouldn't it be really exciting if we could translate those to humans and have an impact potentially on multiple systems? And the question was just, you know, how do we get conviction in what those targets are, especially in humans? Because we're so different from mice and are so different from worms. Right. Which are still one of the standard animals in aging biology. And I was really motivated by the successful examples of using human data to validate targets in other areas of biology. Right. There's like DECODE, which got acquired by Amgen.

3:19There's the UK Biobank, which Pharma has invested a lot in because it's really valuable to see, you know, you've got these 8 billion human experiments going on. You can learn what's already working in the human context and try to apply that for a drug. Right. There's classic genetic examples like PCSK9, which came directly from human data. So the founding idea of BioAge was how do we create a data resource like those, like UK Biobank, like DECODE, but uniquely suited to study aging biology. So it's very much, you know, the platform is sort of based on human longitudinal data with one key difference from those other biobanks, which is really just the length of the follow up.

3:54Right. So UK Biobank decode. You often have people followed for 10 or even 20 years. But of course, the aging process unfolds over decades. And we really wanted to have our initial samples collected from people when they were still healthy, middle aged and healthy, didn't have any overt disease yet. And then have longitudinal data from those same individuals as they aged over time to see if we could find targets, aging targets that predicted future disease risk as well as longevity. And we were able to find some very unique because, you know, while everybody is biobanking today, what you actually need for an aging experiment is someone who was biobanking 50 years ago.

4:30And so that's harder to find that we're able to find some really great biobanks and partner with them and start to build out that data sub. But to your original question, what gave us the conviction was really the fact that it had worked in these other areas, you know, and you really wanted to bring that science and that approach to the study of human aging as well. Well, it's absolutely fascinating. The timeline that you explained is really interesting. Thinking back to 2015, this wasn't something that people in the biotech industry were really talking about with launches. Now I want to fast forward a little bit, actually a lot, just to last month.

BGE 102 Drug Development

5:02So I wanted to talk a little bit about BGE 102. So just last month, you reported positive top line phase one data, and you're describing this as a potential pipeline in a pill. So one oral drug that could address NLRP3-driven inflammation and cardiovascular, ocular, and CNS diseases. So what do you think differentiates this drug from other approaches targeting inflammatory pathways? Yeah, for sure. So NLRP3, it's exactly what we've been talking about. It's like a classic aging biology target.

5:34You know, it's one of these things, inflammation and NLRP3 specifically rise as you go from young to old. And having more inflammation predicts not only, like, increased risk of cardiovascular disease, but increased risk of Alzheimer's, right? It really cuts across diseases, cuts across tissues. So that's why we got really excited about this as a particular target. And as you mentioned, I think inflammation, you know, it's gone through a couple of decades where it's like, is it causal? Is it correlative, right? And then with the CANTOS study with IL-1-β, we saw some of the first evidence that intervening in an inter-inflammation target, IL-1-β, and reducing CRP by a substantial amount to below levels of 2 could really profoundly impact MACE outcomes, cardiovascular outcomes.

6:14So that's, you know, a really exciting hypothesis now. There's, of course, IL-6 drugs in phase three. It's another great target in a related pathway. We work on NLRP3, which, as you mentioned, is a different target. It actually sits upstream of both of them. An interesting feature of that is that when you knock down NLRP3, you're not, you'll be fully knocking down either of those. You're not switching them off the way you would with an antibody, but you are seeing equivalent CRP reductions, which is what, you know, what we think will translate it to improve cardiovascular outcomes. And as to why we chose that target is it's really from the human data sets we just discussed.

6:45So we do see in the large human populations that NLRP3 activation goes up as you get older. And even if you look amongst middle-aged individuals, those individuals who have higher NLRP3 than is typical, while they're not sick with anything yet, they're predicted to live shorter lives and also to have accelerated cognitive decline, which is one reason that we wanted to build brain penetrant drug drugs as well. So we think inflammation matters not only in the periphery, but also in the brain. And one of the other things that is very interesting about BioAge and more recent times, just the set of platform partnerships that the company has.

Platform Partnerships

7:18There's one with Novartis to identify some novel targets at the intersection of aging biology and exercise physiology. And then another with Lily's Explo R&D. I know there's still early stage discovery collaborations, but can you talk about the goals with those partnerships? Yeah, no great question and happy to talk more about that. So as you mentioned, we are a bit more unique where we have some clinical programs, but we also have a lot of activity on our platform. We're really excited to be able to partner on the platform and to continue to grow that resource, right? So just to give you particular examples, with Novartis, they're interested in aging biology for the same reasons we discussed.

7:54And this has changed, I think, in pharma in general in the past decade. I think there's more appreciation of the fact that if you better understand healthy aging, healthy longevity, this could be a rich source of new targets and new biology. And Novartis, like us, they have a lot of conviction in human data and the right human data, right? So as you mentioned, with them, it's specifically a collaboration on the intersection of aging biology and exercise biology. And exercise is still unique. There's a lot of aging and longevity in the popular press these days, right? What's the one proven intervention that actually makes you live longer, that actually delays disease?

8:26It's exercise, you know, cardiovascular exercise or strength training. And what's interesting is that a lot of biology that is key to your body's response to exercise to really realize those benefits declines as a function of aging. So you become less responsive to exercise. You, of course, become less able to do exercise as well. So the goal with Novartis is to find, to basically overlay those targets that are important for the body's response to exercise, to those that are, you know, adversely impacted by aging, to find targets that could be exercise memetics, you know?

8:57And these could be complementary to incretin drugs, for example. I think of those as kind of diet memetic drugs, right? So we have having an exercise memetic component could help with healthy body composition. The company has a program here focused on Apolin, which also lies at this intersection. So the goal with Novartis is that we're, you know, they have some really nice human exercise data. We have our human aging data. We're overlaying the two. It's an interesting collaboration in the sense that the goal is to find novel targets, so targets where there aren't already, you know, drugs in the clinic. It's really new targets.

9:27And here, some of those targets will be advanced by BioAge and others will be advanced by Novartis with sort of milestones and financials owed on either side. And from our perspective, it's great to be able to resource the platform. It's great to be able to have and add this additional bandwidth and capacity to bring forward more of these targets that we think are exciting and emerging from data sets like ours. And now we've taken a look back, talked about some things that are more present, and I wanted to get your perspective looking forward.

Future of Aging-Related Disease

9:54So if you were to look maybe three, four years in the future, what do you think looks fundamentally different about how medicine approaches aging-related disease? It's been interesting to watch the evolution in the past few years really brought forward by the weight loss drugs, right? Because they're reimbursed because they're drugs that prevent disease. And that's a novel idea, right? It wasn't that long ago where people said, oh, you could never, you know, an obesity drug would never be successful. Why would you reimburse for weight loss?

10:24But they're being reimbursed because they prevent disease. And that's, of course, the long-term goal with any aging target. And not to get ahead of myself here, right? So like our NLRP3 drug in the clinic, the first populations will be going after a very, you know, defined disease populations, ASCBD, you know, DME, et cetera, right? But I think that there is the potential with these targets to potentially go earlier in a treatment regime to really prevent disease, potentially even as an incretin combination. Like, for example, that's the phase two population we're about to study right now.

10:55We have top one data for that already now at the end of this year. But that will be obese individuals with elevated CRP. That's half of all obese individuals. Like they have this big risk factor for cardiovascular disease. So I think in the future, there could be the potential to go earlier, right? And what we're going to require there, so it's, I don't think aging itself will be, you know, necessarily recognized, you know. But what we could see, though, is biomarkers for these aging mechanisms like inflammation, right? Like I would love to see CRP become a surrogate endpoint, like cholesterol, right?

11:26So that's the kind of thing I think we can see some evolution forwards. Some of these key things that you might want to reduce aging damage, like inflammation. It's definitely an extremely exciting space to watch, has a lot of attention. And Kristen, I just want to thank you for joining the Top Line and sharing some of your perspective today. Yeah, thanks for having me.

11:48That's it for The Top Line. I'm your host, Ayla Ellison. You can find out more about this topic in our show notes at fiercepharma.com. Look for podcasts. And that's the bottom line from The Top Line.

12:03Thank you.