James Peyer is the Chief Executive Officer and Co-Founder of Cambrian Biopharma. He also serves as the Chairman of the Board of Sensei Biotherapeutics and board and executive roles across Cambrian’s pipeline. He has spent his entire life dedicated to the mission of finding ways of preventing people from getting diseases like cancer and Alzheimer’s instead of waiting for people to get sick.
Nathaniel David has co-founded four biotechnology companies that have collectively raised over $2 billion in financing and have given rise to three IPOs, two M&A acquisitions, and four FDA-approved medicines (ALOGLIPTIN, TRELAGLIPTIN, ZEMDRI, and KYBELLA). Nathaniel holds 46 allowed patents in fields as far flung as nanovolume crystallography, antibiotic resistance, aesthetic medicine, and cellular senescence.
Kristen Fortney is the co-founder and CEO of BioAge, a clinical-stage biotechnology company developing a pipeline of treatments to extend healthy lifespan by targeting the molecular causes of aging. The company uses its discovery platform, which combines quantitative analysis of proprietary longitudinal human samples with detailed health records tracking individuals over the lifespan, to map out the key molecular pathways that impact healthy human aging.
Moderator Dina Radenkovic is a Partner at SALT Fund. Dina is an academic doctor and medical technology entrepreneur. She qualified with a dual degree in medicine and physiology from UCL Medical School. Dina is a co-founder and CSO of Hooke, an elite longevity research clinic, in collaboration with the Buck Institute for Aging.
SPEAKERS
Kristen Fortney
Chief Executive Officer
BioAge
James Peyer
Chief Executive Officer & Co-Founder
Cambrian Biopharma
Nathaniel David
Chief Executive Officer
Jupiter Bioventures
MODERATOR
Dr. Dina Radenkovic
Partner
The SALT Fund
TIMESTAMPS
EPISODE TRANSCRIPT
Dr. Dina Radenkovic: (00:07)
Well, welcome everyone to another Longevity Panel. And this time we're going to focus a bit on biotech. How do we set build successful biotech companies in the field of aging? And then how do we invest in the age of aging, as I like to call this period where we have long living, but not necessarily healthy population. So I'm joined on stage by James Peyer, the founder, CEO of Cambrian Biopharma. Nathaniel David, who is a serial biotech founder, and also founder of Unity, a biotechnology company, and Jupiter. And then Kristin Fortney the founder and CEO of BioAge labs. So I guess the best way to start perhaps would be, why don't you all give us a very brief introduction about your companies and what is the single thing that your company is doing that you're most excited about. Ned, I guess, would you like to go first?
Nathaniel David: (01:01)
Sure. So I'll talk about, thanks, Dina. And so Dina mentioned that I'm a serial company builder. So I'll just talk about, and I've been doing this for about 22 years, four approved medicines. Two of my companies, Unity is a company that makes medicines that eliminate old cells. These are cells that don't divide anymore and they drive a bunch of disease. And we tried it first in arthritis in human beings, didn't work there. It was a pretty big clinical failure there. And then we moved into diseases of the aging retina and we have beautiful data happening there where when we dose a patient with a disease of the aging retina, they can gain within 24 hours as much as 20 letters on an eye chart, like at the DMV. So that's really cool, that's Unity.
Nathaniel David: (01:53)
And brand new company we're starting called [Cavalry 00:01:56]. What we're doing is we're taking growth factors, these are things that float around in your body and tell your tissue what to do. And we're putting little zip codes on them so we can send them, so they swim to very specific spots. And we have one that we're building that can swim into the plaques in your arteries, functioning like a molecular stint. And we're building another one that can swim into your muscles to treat various muscular dystrophies. And a similar one for bone. And we call those molecules cupids. And they're pretty cool.
Dr. Dina Radenkovic: (02:29)
Yeah, I love the cupids. Kristen, tell us a bit about BioAge.
Kristen Fortney: (02:33)
Thanks, Dina, for having me here today. So BioAge is a clinical stage biotechnology company developing a pipeline of therapies that treat diseases of aging, and that ultimately might help extend the healthy lifespan. So we currently have three different programs in the clinic. Our most advanced one, so that's probably the most exciting piece of data right now. It's right in the middle of a phase two trial. And this drug we think rejuvenates certain aspects of immune aging. So in particular, as you get older, if you're challenged with pretty much any virus or bacteria, your dendritic cells don't migrate as well to where they're needed to wake up your T cells. And this drug can correct that. And so it can help improve your response to the flu, but also to COVID, which is clearly a disease of immune aging. If everybody here has the immune system of a 20 year old, it would be a very different pandemic.
Kristen Fortney: (03:21)
So that first trial was that drug where we're in the middle of the phase two, it's an older COVID-19 patient population that's hospitalized that we're going into. And these are people who still, 30% of these people because of their age are progressing to really poor outcomes like ventilator or even death. We have two additional programs that are in clinical stage right now, focused on muscle aging and really a pipeline of therapies. We want to bring several more clinical programs up forward over the coming years. And another important point to mention about BioAge is that all of these programs is different mechanistic bets on these molecular biology of aging are coming from our human data platform. So we have invested a lot in understanding how humans age from middle-age and onwards to death, and that's where our discoveries and our pipelines and our targets are coming from.
Dr. Dina Radenkovic: (04:14)
And James, Cambrian.
James Peyer: (04:16)
Thanks Dina. Thanks everyone for coming in. So I run a company called Cambrian, which was created to capture a bit of a promise of this longevity biotech industry, which is really in its infancy but a pretty exciting infancy. And so I've spent most of my career working with academics from around the world who have made a key discovery that can extend the healthy lifespan of an animal, usually a mouse. And figuring out with them, how do you take that discovery in a mouse and build it into a human medicine. And so Cambrian has created a whole series of subsidiaries. We have 12 different companies under our umbrella advancing 14 different programs, each of which has already shown that it can impact both a fundamental pathway in aging and another disease in mouse models. And now those programs are marching towards the clinic. And we're kind of along this path where we're bringing between five and eight new scientific discoveries under our umbrella every single year, which is a fun place to be.
Dr. Dina Radenkovic: (05:29)
A few things that we're going to dive deeper later on in discussion that you've mentioned, but that's just basically an overview. Should we start with giving a bit of background on aging. So even going into aging as a clinician, right. Going from, oh, we want to prevent heart disease. And then I just ended up, oh, heart disease is actually linked to the immune system. So why didn't I devote my career to actually preventing the causes of the causes. So all of you are creating drugs that address these causes of the causes. All of you are addressing aging in one way or the other. Could you tell us why does aging even happen? I don't know, Ned, what are your thoughts?
Nathaniel David: (06:08)
So first I'll just say, as a scientist, we do not know why we age. For example, a mouse lives three years, a human 85 years, a Greenland shark, 400 years. We do not have any real idea why these differences exist. And we are clearly missing something very big. But if you ask me what do I think? Okay, so I'll express why I think we age through a movie metaphor. So I don't know if you guys have ever seen this 1970s movie called Gray Gardens. It's a movie shown at the Cannes Film Festival. And it was this movie about these aging socialites living in this house that used to be this grand house out in the Hamptons. And they lived there for 50 years in ever increasing poverty and they never repaired anything. So after 50 years of this, they're hanging out and they're raccoons that are now living inside the house, feral cats live there, it's infested with fleas. The water doesn't work and there are holes in the roof. The health department was trying to evict them.
Nathaniel David: (07:29)
So why am I telling this story about a 1970s movie? Well, I think aging is a lot like that house in Gray Gardens. If you look at biology as we age, at every level of organization from the very lowest level where your DNA sequences to the very highest level of organization, when you look at an old person and what you see with your eyes when you look at them. If you look at your DNA, it mutates as you age throughout your body. If you click up another level of organization, you see that the cells that are centrally encoded by your DNA, you begin to lose them. You actually have fewer cells as you get older which is a little disturbing. Click up another layer to the layer of tissue organization, your tissues, which when you're young have beautiful organization. If you look in the retina, the retina of a 20 year old has these beautiful structural divisions between the various layers within the retina, which are lost as you age.
Nathaniel David: (08:34)
Or if you look in skin of a young person, which is defined with these beautiful demarcations between the epidermis and dermis. As you age, it becomes this chaotic undulating landscape where you can't even tell the difference anymore. And if you look at the highest level, when you simply look at an older person and you see the performance loss and all of the hallmarks you think of as aging, that you see disorder there as well. And I think that like in Gray Gardens, biology never figured out how to resist disorder. It never figured out how to resist it or how to reverse it because it was never selected on. But clearly the Greenland shark knows something we don't know about resisting disorder. And if we knew, I think we could start to build tools that would do that.
Dr. Dina Radenkovic: (09:24)
You want to make a comment?
James Peyer: (09:25)
It's an interesting point to leap off of. Ned mentioned, we just didn't evolve this. It's I think really important to remember in this space that the major killer of humankind was not these diseases of aging until the 20th century. And so the fact that we are as a society grappling with them is still a relatively new phenomenon compared to our ancestral and evolutionary predators, the infectious disease, right. And so we were programmed in some ways by evolution or selected for an evolution to become healthily into our reproductive ages. And then after that there's like some benefits of growing a little bit beyond that, but not huge ones. And so now this engineering problem that we have is like, okay, can we add in what evolution would have liked to do, but wasn't being selected for hard enough. Can we figure out those mechanisms and put them into a much more long lived society, which is what we're all becoming.
Dr. Dina Radenkovic: (10:27)
Fascinating, couldn't agree more. But anyway, I think where we want to take this panel forward is really provide the audience with some tips or like, what is a good longevity company. So let's structure it in three parts. Let's talk about the measuring things, how do we assess a good longevity acid. Then let's talk about the structure of a longevity company. And then perhaps about the computational approaches, proprietary data sets. If for example, BioAge has been pioneering to create a longevity company of high value. So James, let's start with biomarkers and perhaps we could talk about this further. People always talk about, oh, it's very difficult to do clinical trials of aging because how I'm going to follow up people over 50 years and then find out in 50 years time if this is going to affect their aging.
Dr. Dina Radenkovic: (11:14)
And then we talked a lot and there's been a lot of research about developing some surrogate biomarkers. So things that can tell us in only a short period of time how one's biological age is changing. But we ended up having, we are having different clocks, but not a single one has been validated. Do you think that a longevity company needs to invest in this biomarkers? And then what is Cambrian doing in this bioinformatics biomarker space so that we're able to actually conduct trials so that we can show aha, this intervention over this five-year trial affects aging and will extend your life if you take it for 20 years. And you're going to get, I don't know, 35 years of extra healthy life expectancy.
James Peyer: (11:56)
So the short, short answer to that question is yes, but just giving a little bit more data there and to reemphasize the point, the fundamental challenge of building a company in this emerging longevity space is what Dina just mentioned. If we chop the room in half and gave half of you an experimental aging drug and put half of you on a placebo, what do we expect that drug to actually do? We expect that people's house would grow into disorder slower, right? And we'd get less cancer, less Alzheimer's disease, less muscle weakness, all of these things that happen as we age. But if this was our experimental group, how long would we have to wait to see all of those changes start happening?
James Peyer: (12:40)
And so, as Dina mentioned, there is a way in developing medicines that can help us get around that problem and not have to wait for 15 years. And that is by developing a surrogate biomarker of age related disease risk. And this is something we don't know exactly what this will be yet, but this is going to be the fulcrum point where you change from a whole bunch of interesting medicines built on pathways and longevity to an industry that I think will eclipse the rest of the pharmaceutical industry. And so in my view, each longevity biotech company has to have these two things in mind. First, how do you take medicines that target fundamental pathways in aging, show them to be safe, effective, and get them on the market in some disease today. And secondly, how can you lay the foundations for this inflection point that will come to dominate how we think about medicines for the deadliest diseases of our time.
Dr. Dina Radenkovic: (13:40)
Fascinating. And I guess going back to the structure of this longevity company that we're all hoping for and hopefully multiple companies. And we also invest at SALT in some of these longevity companies. So how should this company be structured? Should it be a single company that has got multiple clinical programs? Should it be a distributed company, more like an LLC structure with multiple subsidiaries? Kristen, could you tell us a bit more about how you set up BioAge and which model did you choose for. And which model do you think is the best one? And there are pros and cons that we will discuss together.
Kristen Fortney: (14:14)
I mean, that's a challenging problem. I think what is the optimal model in biotech, and I think it's evolving. It depends as a function of what the investment climate is, but also what your strategy is as a company. And in our case at BioAge, all our targets are coming from our platform and we've invested a lot in really the human datasets to evaluate the targets, to do risk our clinical indications, but also just the really old mice that we use to test out all our interventions in the common indications that are our focus areas. So leveraging those over and over again, we're going to be a platform style company which has worked out well for a lot of other, I would say, comparables in our space like Recursion and others, [Denali 00:14:55], yeah.
Dr. Dina Radenkovic: (14:57)
I guess people often say could be easier to go public if you concluded everything, but how do you even stratify. And Ned, you've done both. Can you tell us a bit about your experience? You've been in both worlds.
Nathaniel David: (15:09)
So I wish I knew what was best. We are in the midst of lived experience right now, but I've, over the last 22 years, all the companies I built were normal. When I say normal, meaning you set up a C Corp, you divide up stock, you put people in it, you raise money. And that seemed to work well enough. Jupiter, my new vehicle is actually set up much the way Cambrian is set up where it's a structure where we have a sort of top co on top with, well, with Jupiter of course it has moons. So every one of the companies we start actually begins with a moon of Jupiter name, there's lots of moons of Jupiter, 79 at last count. So we've got a lot of names we can work with. And so we're giving that a try and I think actually James has a really good explanation as to why this works. James, you want to talk about the academic?
James Peyer: (16:05)
Yeah, sure. I'll jump in. So my general view on the biotech space broadly, not just the longevity world, is that discoveries coming... Most discoveries are coming out of universities at some point. And those discoveries are going to fall into two broad types of categories. Discoveries that create a platform that allow you to make a number of other fundamental discoveries. This is kind of what BioAge has, a platform company. And then individual breakthroughs that lead to a single opportunity to make a drug, a single hypothesis, but that has binary risk, right. Where you're going to, it's either going to work or it's not going to. And my view is that these are going to develop into two types of biotech companies that can live on the public markets. One is these platform companies like Moderna, a lot that we've seen in the biotech space today. And then another are what I call engines, where it's more about how do you source and operationalize these individual discoveries from around the world and then wrap them together into a single risk diversified entity. And that's what Cambrian is.
Dr. Dina Radenkovic: (17:14)
And could you elaborate a bit more about that, about your holding companies, subsidiaries. How you put it together because some traditional biotech investors would say, why would they invest in such a holding company because I'm essentially paying fees and fees. If the biotech fund invest into a holding company and then the holding company goes and acquire assets, why would I go for substructure? And what we're seeing right now in this world of biotech, an agent needs really this intersection off, it's kind of taking a step back, it's cross hybridization of multiple fields. So we have different set of investors and we've got a lot of tech investors and they're more open in this structure. For them it's like, okay, I understand this model. We can fail and iterate quickly, I like it. But biotech investors are still very cautious. So what do you say about that? And how have you created that system that it goes smoothly and you have multiple subsidiaries? Give us a bit more color there.
James Peyer: (18:06)
And I could talk about the financial engineering here until we all would hope for some aging drugs, but let me kind of just be general on it. I think that the fees on fees argument doesn't actually play out when you're operating these companies. So I used to run a VC fund before I started Cambrian. And we took, as one of our principle financial objectives, all of the fees that you would pay a VC fund plus all of the salaries and so on that you would pay to an executive team to run all of these different assets if you wanted to make individual bets. We can run their company for about 75% of what this would be, and then eliminate a lot of that extra management layer. In some ways, the inefficiencies of single VC bets. And so I think that that doesn't really hold water when you get down into the operation of these companies.
James Peyer: (19:02)
And then secondly, one of the big challenges of early stage biotech companies is finding a team that knows how to develop drugs. Academics are trained to make breakthroughs. It's different teams that are trained to develop drugs. And so building a centralized expert team that knows how to work with academics to bring those drugs forward is the differentiator between many of the companies that make it and many that don't. And it has been, you can get incredible people who you can deploy extremely efficiently in one of these roll-up models. I think that's part of the reason that I've really fallen in love with the structure.
Nathaniel David: (19:40)
I will say Dina, though, that this structure definitely gives the classic sandhill road, biotech VCs, sort of a conniption fit. And my classical, the VCs that I've invested with for years, Arch and Venrock, they don't want to invest actually in Jupiter. They want to invest in Jupiter's moons. And that works okay too, okay. I will say also there's no fees in our model because every single dollar that winds up going into Jupiter, winds up being converted into ownership in the moons. So there's literally zero. That was 100% capital efficient.
Dr. Dina Radenkovic: (20:20)
Fascinating. Well, I think the Biden model does need to change because we do need to remove that binary risk of finding true love. It might work, it might not. Kristen, what about the IP? So if we are just starting a longevity company, and again, how we're assessing longevity company. You started with a lot of proprietary data, and then you have managed to acquire clinical assets and really accelerated. I mean, it's extremely rare to find longevity biotech that has got two clinical assets almost. Do you think that that was the key? And how did you do that?
Kristen Fortney: (20:55)
Yeah, sure, great question. I mean, our whole approach at BioAge is aging is really complicated, right? You've heard that today. There's all these different things that are going wrong, and from the panel earlier. And we believe that, our thesis is that we want to learn from what's already working. And what I mean by that is that there were already all these human experiments and they're people that are living 90 or 100 plus. Their brains still work. Their bodies still work. What's different about their biology that we can learn from. And so at BioAge we've invested a lot in mapping out how humans age. We've made a number of special relationships with biobanks, where we have proprietary and exclusive data that started, they are very special biobanks. They started collecting samples from middle-aged people as long as 50 years ago. So there's like blood that's been in the freezer 50 for years. Collected longitudinally, and then coupled to health records that track these individuals for the entire rest of their lives. And so that's our starting point, right.
Kristen Fortney: (21:50)
And what we do is we go into these samples, we enumerate every molecule in there with modern technologies. That's thousands of proteins with the proteome, thousands of metabolites, tens of thousands of RNA transcripts, make a big list of stuff. And then from these data sets, you can ask a whole bunch of questions. So you can say, what's changing with age? But even more importantly you can say, what is predicting the future? What is different about those 50 year olds who are going on to live 90 plus with great muscle strength, with cognitive function from the rest of us, and start to build a map of those differences.
Kristen Fortney: (22:21)
And that's the science that underlies what we do. And as you might expect, because so many different things are going wrong, there are several dozen important pathways for aging. And then from that point onward, because aging is a new space, it's in biotech, it's hard. We want to start with the most de-risked programs possible. So we started with the intersection of these pathways that are important for aging in the human data, with the clinical assets that are already out there because there's a lot of risk in developing a drug and taking it through R&D, taking it to that first clinical trial, even looking at the safety signal. So our criteria for our first set of drugs, while it's have already been in a phase one, you have to know that it's already safe. You can know that it hits its target. Then we can go immediately into a phase two, proof of concepts study, an important agent indication. And we're making three such clinical stage bets today. And I'd like us to make as many as 10 over the next couple of years.
Kristen Fortney: (23:12)
An important point too, right, I think that's the first wave of targets emerging from our data sets. It's going to be these ones where the clinical stage assets exist. Then we can start to look at the assets that are near IMD and we can start to work on discovery programs. An important point too I I think, especially in the context of academic sciences, one reason we love our human cohorts is because we think it's like a human overlay on all of what's known about aging biology, right? So there's going to be a lot of things that are really important for how a mouse ages or how a rumor fly ages, which is really still the focus of academic science. And many of those are just not going to matter for us. Mice, for example, die exclusively of cancer. Heart disease is not a bottleneck to their lifespan. Alzheimer's never happens, which is why they've been a terrible model for Alzheimer's drug discovery.
Kristen Fortney: (23:57)
So we like being able to use our human data to say, like most, and I can tell you, right, most of the things that work on animals, you don't see human signal. And that doesn't mean that they're not going to work, but it just, they're much less compelling than the ones where you see a massive human signal. So for example, the drug that we brought in most recently from Amgen, it's an agonist of apollon receptor, apollon is an exokine that circulates in your blood. There was a nature medicine paper from one of our collaborators a couple of years ago, showing that it can increase mouse health span. So it actually, if you gave it to older mice, they ran better on their wheels.
Kristen Fortney: (24:33)
But then when we looked in our human data, you saw this really strong signal where if you had higher levels of apollon in that middle age, you're living longer, your brain works better and longer, your muscles work better and longer. And that's the kind of data package we really lik to see. And the way that we work is we see the human signal, then we reach out to a company to get an asset and we stick it into our in vivo models. So we did a whole bevy of muscle aging models in mice with Amgen's drug. And we are very excited by the results, and we're going to start that trial in after a few months.
Dr. Dina Radenkovic: (25:04)
Absolutely. And you've touched on a very important topic and which is clinical trials. Regardless of how excited we are about aging, aging is not recognized as an indication by the FDA. And a drug needs to pass through trials and show some results in order to be approved, in order to be licensed. So often a challenge of these companies is, what indication, what disease should I almost pitch this drug to so that I can have a good trial and then my drug will be in the market. And then we can potentially use this drug to cure other things and potentially be used for prevention of aging. Ned, I think you do need to tell a story there about how did you struggle once you identified a scientific pathway with indication and how you managed to find the right indication. And how should longevity companies think about conducting clinical trials.
Nathaniel David: (25:59)
So I come at this question pretty differently than James, probably more similar to the way Kristen thinks about it. So I'm a drug hunter by trade, okay. I don't necessarily try to cure aging. I use aging to help discover drugs. And so the way I came at this was really with the grain in terms of how FDA and similar agencies want us to discover drugs today. Which is pick a disease that you can point at, that you know people suffer from, and make a medicine for that disease. Hey, if it impacts aging, great. But please don't talk about it, right? And so that's the approach we took at Unity, going after first, arthritis, which is the primary reason it hurts to be old. I would say that's pretty close to aging. And then of course, diseases of the aging retina.
Nathaniel David: (26:59)
And so we shied away in a very intentional way from trying to use some sort of biomarker of aging and stuck squarely to diseases of aging. I think that an agency like FDA which views itself primarily, and it's in the DNA of the organization, as a protector of the populace. After all, they started regulating food before they did drugs. And the notion that they would allow you to make a medicine that would impact the very slowest thing that happens to us, which is aging, is just against their DNA. It's against their culture. Now, will that change occur? Sure, maybe. But I think it's a very uphill battle. And I think it's a really tough slog.
Dr. Dina Radenkovic: (27:52)
I see.
Kristen Fortney: (27:52)
I'd like to comment here too actually, because this is probably, it's drug developers and aging, it's like a central topic, right. How do you actually, if you believe you have an aging drug in your hands, like in our case, it's rejuvenating muscle, rejuvenating aging, how do you get the most out of that? And in our case, we're committing to mechanisms that we think ultimately could be safely administered to a large population chronically. We've made those decisions so far, but yes, you have to start with an acute indication that's a real disease because otherwise it's a hard road.
Kristen Fortney: (28:21)
We're trying to have the best of both worlds by going to town on secondary end points, right, because we're giving our drug, which we think is addressing an aging mechanism in a specific disease context. But we want to know, are we also slowing their aging? So we're very interested in collecting like omex biomarkers and using wearables to collect motion data and learn as much as we can about the aging of these people as well. Hopefully it's like to guided indication selection, right. There are a handful of examples, like statins which are prescribed like an aging drug today, right. But which had that more narrow start indication labeled, widening over time. And I think we can learn from this.
Dr. Dina Radenkovic: (28:57)
We can use it as a way in and then expand the indications. And I guess the final question, this is still an audience that actively invests and supports new technologies. What single technology or breakthrough that you think will happen in this decade are you most excited about and you think will have an impact of human longevity. Who wants to go first? It's a difficult one. All right, Ned.
Nathaniel David: (29:21)
So this decade?
Dr. Dina Radenkovic: (29:22)
Yes.
Nathaniel David: (29:23)
So it's going to be how to properly dose rapamycin. So rapamycin is a drug that's approved in the United States for, believe it or not, when you get a kidney transplant so you don't reject it. So you take this drug every day and it tamps down your immune system. Now, turns out this drug given at a much lower dose, about one seventh of the dose, will extend the lifespan of rodents by 30%. And it works in flies, rodents, every species we've tried it in, this drug works. And this, but no one knows how to dose it. And no one really even understands why it extends life. It's a mystery. But figuring out a safe and efficacious dose of this molecule is going to happen this decade. And it's going to be something that will, when figured out, be used by tens of millions of people.
Dr. Dina Radenkovic: (30:25)
Fascinating. There were actually studies and we mentioned that rapamycin or rapamycin analogs might even be used as immune boosters together with effect vaccines. So it's something that I think has accelerated an interest into the field as we battled through.
Nathaniel David: (30:41)
Yeah, there's an extensive literature using rapamycin, both in humans as well as in animals. In which your response to vaccination doesn't go down as you might intuitively think, but goes up. Again mysterious as to why.
Dr. Dina Radenkovic: (31:00)
James?
James Peyer: (31:02)
So I guess I'm going to, it would be fun to just talk about rapa for a while and we could have a panel just on that. But I'm going to depart a little bit and say, talk about the biggest innovations in this field, I think that they're actually organizational and strategic as opposed to scientific. I think that the last decade saw enough scientific breakthroughs in this aging space to fill an awful lot of corporate pipelines. And all of those innovations addressing the question of how you take these fundamental insights into pathways of aging biology, and get those into human clinical trials, that's the experiment that in some ways the three of us are here taking different shots on goal at, taking different, I think very thoughtful, strategic approaches to building big biotech companies addressing this space.
James Peyer: (31:53)
And then somewhere around the end of this decade, there's going to be this strategic inflection point. And in my view, as Ned was just talking about, it's going to be around the time that the FDA or if the US is too slow and too conservative, another regulatory agency elsewhere in the world takes the plunge and allows companies that have safe and effective drugs that target an aging pathway to be tested in healthy people with a short surrogate endpoint clinical trial. And the moment that happens, the world starts to change forever. And I think that that can happen this decade.
Dr. Dina Radenkovic: (32:27)
It would be like [inaudible 00:32:28] and Bitcoin. We have to give Kristen a chance to answer this question.
Kristen Fortney: (32:32)
Yeah, for sure. So I mean, the kinds of enabling technologies that I'm the most bullish on are really these genomic scale technologies to interrogate and also intervene in biology. And, for example, that's what BioAge uses with proteomics and human cohorts or that's what a CRISPR screen is, right. And the reason why I think these are so important is because they allow you to brute force what are otherwise, incredibly challenging problems. Like Ned mentioned, we still don't actually know how rapamycin works, right. But it does work. And it's a matter of figuring out how to dose it. And if we could, I mean, whenever someone is doing an exome scale experiment to find a PCSK9, or another genetic variant that predisposes to, protects you from disease, it's the kind of a brute force in experiment.
Kristen Fortney: (33:14)
So now that we have these technologies and the AI and the computation to analyze these data sets for millions of points, I think there's a lot of really important problems in aging we can apply them to. And again, I'm a big believer in copying what already works, right. So bowhead whales, Greenland sharks, they're doing something different. We have the tools now to figure out what. Even epigenetic reprogramming, right? These are the tools that are going to teach us how it works. So I think the space is going to get a lot bigger.
Nathaniel David: (33:39)
Well, I was just going to say that it would be hard, well, much of what you said is true. There's all this stuff we can work on to make medicines out of. But the notion that that could be more exciting than knowing why a Greenland shark lives 400 years, that stretches it, I think. Because, I mean, when we start to piece that narrative together, oh my Lord, think of what we will be able to do.
James Peyer: (34:09)
I'm with you. I mean, as a scientist, nothing gets me more jazzed about that. But I think that the inflection point for this field is not going to be finding the next rapamycin or the next, whatever's driving the 400 year lifespans of the Greenland shark. It's to create an ecosystem where everyone in the world cares desperately about that problem. And I think that if we hit that inflection point, we enter a world where it's not just like the folks up here that know all about this, but all of you guys are thinking every single day about what that next scientific breakthrough that's going to elucidate how the Greenland shark lives to 400 years, because it will affect your lives in the impending future. And that I think is where I want to push this space. And I think that's where we're going to see stuff this decade.
Kristen Fortney: (34:59)
Well, the first approved drug for aging, I think it's going to be such an important milestone, right. It's still such a tiny field. There are a handful of biotechs, we are probably most of them. Clinical or near clinical working on aging and, but there are dozens of mechanisms that could be brought forward that could extend health span and lifespan. And I think that yes, getting that first program through which is probably already exists either in academia or the clinic is going to be transformational.
Dr. Dina Radenkovic: (35:24)
Well, the creation to a creation of a longevity ecosystem. And thank you everyone for the life of this question. And thank you to the audience for listening in.