- 2 years ago
James Peyer is the CEO and Founder of Cambrian. Peyer's goal with his pharma-bio company is to create healthier drugs that lengthen lifespans and improve overall health in individuals. Peyer was previously Managing Partner with Apollo Ventures, the first global longevity-focused venture capital firm. He is a graduate of UT Southwestern (National Science Foundation Fellow) with a PhD in blood and stem cell biology.
James and Diane Brady speak at Founder's Forum about Cambrian's newest business developments, timelines of producing Cambrian's products and how a healthier lifestyle holds as much influence as good medicine.
James and Diane Brady speak at Founder's Forum about Cambrian's newest business developments, timelines of producing Cambrian's products and how a healthier lifestyle holds as much influence as good medicine.
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LifestyleTranscript
00:00 Hi, everybody.
00:03 I'm Diane Brady.
00:04 I'm here at the Founders Forum with Dr. James Pyer, who is the founder and CEO of
00:09 Cambrian Bio.
00:10 Nice to see you.
00:11 Hey, Diane.
00:12 Nice to see you, too.
00:13 I want to go back to the very beginning, because you had a venture fund that was involved
00:18 in sort of helping scientists to basically commercialize what they were doing, right?
00:22 So take us back to what did you want to be when you grew up, because you have this fascinating
00:27 company now.
00:28 Well, so it started for me on, I guess, a bit of a somber note.
00:33 When I was a teenager, my grandfather died of cancer.
00:37 And as I was watching him get sick and ultimately die, I decided, or I observed, that the treatments
00:46 that he could get had really no chance of saving his life, maybe just extending it a
00:51 little bit.
00:52 Yeah, in agony, too.
00:53 In agony, right?
00:54 In a place of suffering.
00:56 And at around that time, this was now close to 20, 25 years ago, we were just starting
01:03 to make scientific breakthroughs in animals, right?
01:06 Worms and flies, not even really mice yet, where you could change one gene.
01:11 This is after we'd mapped sort of the-
01:15 It was right as that was happening, right?
01:17 Right as we were sequencing the genome, we were getting all of these new tools to do
01:21 molecular biology for the first time in living organisms.
01:26 And we could change one gene and double the lifespan, healthy lifespan, of an animal.
01:31 And I was like, that's the future.
01:33 Not just waiting for someone to get sick and then trying to deal with a complex disease
01:38 like cancer, but preventing it.
01:40 Which would take somebody into medicine, but not necessarily into finance and venture funding.
01:44 That's fair.
01:46 And so, yeah, so I spent the first part of my career as a PhD scientist, right?
01:50 Doing research in mice.
01:52 And what happened in this field is that people would make these discoveries where you could
01:58 extend healthy lifespan in an animal.
02:00 And then the big investors and pharma companies would say, "Well, you can't run a clinical
02:04 trial for aging because aging is not a disease."
02:08 And so go back to your labs and play with your mice.
02:10 And I said, "That can't be right."
02:12 Because this field that was making all of these discoveries, they were doing something
02:17 so impressive.
02:18 They were preventing cancer and muscle weakness and metabolic decline and dementia all at
02:27 the same time with one tweak.
02:29 And I was like, "There has to be a way to turn that into a drug."
02:32 And that's what got me into the finance side of the game.
02:35 So I left academia, started this venture firm, which was the first group, which is called
02:39 Apollo Health Ventures, which was the first group to help scientists that had made a discovery
02:44 about aging biology turn that into a company.
02:48 And that worked so well, I got to do not just an early stage venture firm, but I got to
02:52 create Cambrian, which is itself kind of like a combination of an early stage VC fund and
02:57 a pharma company that can help those scientists not just take the first step going out of
03:02 the lab, but actually take the follow-on steps to turn that discovery into a drug and now
03:07 do human clinical trials.
03:09 So you're doing so many cool things at Cambrian.
03:11 And I want to unpack a little that transition from being a PhD scientist to a venture capitalist.
03:19 How did you do it?
03:20 Because did you have access to a lot of capital?
03:22 Did you go to Silicon Valley?
03:23 I mean, I think it's very aspirational.
03:26 A lot of people probably would love to do it.
03:28 It can't be that easy.
03:29 So when I finished my PhD program, I had never heard of a venture capitalist.
03:33 Congratulations.
03:34 No, I'm just kidding.
03:35 I had started a small education company because I knew eventually I wanted to develop drugs.
03:39 Didn't have any drugs as a college student.
03:40 So I started a small company that I built without any VC, without any investment money.
03:47 But my secret was always just being very loud.
03:50 And so I had this idea in my first job in consulting after my PhD.
03:56 I had this idea that we could take these discoveries and turn them into traditional looking biotech
04:01 companies but with the potential for preventative medicine.
04:04 Right.
04:05 And I just told everyone that I could out of it.
04:08 I just told everyone that I could about it.
04:10 And after about a year, friends of friends of friends, this kind of got through a network
04:15 and someone came back to me and said, "Hey, we just sold a company.
04:19 We think that aging is going to be the next big thing.
04:21 We heard that you're the guy to talk to."
04:24 And that spiraled into an opportunity to move to Germany and start that fund with these
04:30 two amazing guys, Nils Regge and Ola Mensching, who were my partners.
04:34 Talk about Cambrian right now.
04:36 First of all, sort of the genesis of this and you've got some exciting drugs in development
04:40 too.
04:41 But let's start with the beginning.
04:43 So Cambrian, we started four years ago.
04:46 It was myself and a successful German investor.
04:51 Not actually the guy I worked with before, but a guy named Christian Engermeyer, who
04:55 is really well known for his role in kickstarting the use of psychedelics to treat mental health
05:01 disease.
05:02 He was the founder of all of those companies and his next big thing was, "Okay, if we
05:06 can treat mental health with psychedelics."
05:08 Now that we're connected to the earth, now what?
05:10 How long can we last?
05:11 Now can we live healthier longer?
05:13 And so Christian and I started Cambrian together with one of my colleagues from McKinsey.
05:24 And originally it was very small.
05:26 We had a few scientists who were going to do this journey with us and take drugs forward
05:32 from academia all the way to humans.
05:34 Fast forward four years, we've been able to raise about $200 million.
05:38 We have more than a dozen subsidiaries and more than a hundred people working across
05:45 a whole bunch of different mechanisms that we can touch on a little bit at Cambrian.
05:50 But the most exciting of these, there are really two stories.
05:53 There's really 12 stories.
05:55 But the one most exciting story that I think is so fun is that we are now in human clinical
06:01 trials with a drug that can, at least at a high level, turn on our metabolism and ramp
06:10 it up sort of to the levels that we experienced when we were a teenager or a 20-something.
06:15 So it's like we're running when we're sitting down?
06:18 In effect we can eat more, exercise less, and lose weight?
06:22 What is the net impact of this?
06:24 So this is where I have to be really careful.
06:26 Okay, because you're in trials.
06:28 Because we're in human clinical trials and I have to just disclaimer, disclaimer, disclaimer
06:32 this because most of what we know about these drugs are from studies in mice and dogs and
06:39 rats.
06:40 We're starting to get data in humans, but most of the data we have in humans is just
06:44 that it's safe to give.
06:47 And that seems to be the case so far, but even that is preliminary.
06:50 So this is-
06:51 So it's a molecular, you're changing something in molecular level to increase our metabolism.
06:57 Is that it or is it doing something else?
07:00 That's right.
07:01 So with disclaimers out of the way, to get to the molecular mechanism here, there is
07:07 a sensor in all of our cells called AMPK.
07:12 And this AMPK sensor detects the amount of energy reserve that we have in our cells.
07:18 And when we exercise, that energy gets depleted, the sensor gets turned on.
07:23 And so this drug that we have, it's called ATX304, which is its code name for right now.
07:28 This drug turns on that sensor, even if you haven't depleted the energy levels first.
07:34 And when that sensor gets turned on, it will increase the metabolism of the heart and the
07:39 muscles and it will burn fat and all of these sorts of things.
07:42 So just like you're saying, we've been able to give it to mice and the mice are able to
07:48 increase their cardiac capacity.
07:50 They can run longer on a treadmill, even without any training.
07:54 You can put them on a high fat diet and they will lose weight.
07:57 And it seems to be mostly body fat, mostly fat that they lose while eating more because
08:01 their metabolism has amped up.
08:03 That's interesting.
08:04 Now, one of the things about being a teenager is you also, your muscle mass, the strength.
08:08 Is it too early to tell whether it's actually making our bodies younger, not just slimmer?
08:15 So what I will say is that there is evidence in animals that the whole body behaves better
08:23 when you have regular activation of this pathway.
08:26 Not just, it's not just slimming down.
08:28 It's not like the obesity drugs on the market today, for example.
08:31 That make your face look gaunt because you lose weight so quickly?
08:34 Exactly.
08:35 Because that's kind of like you're fasting, right?
08:37 It makes people less hungry.
08:38 They eat less food.
08:39 This is different because it's ramping up metabolism.
08:42 It's way too early to say what the health benefits and the effect on muscle and these
08:46 sorts of things are, but it looks pretty exciting.
08:49 So I want to step back a second because I think what's interesting, let's talk about
08:54 the societal benefits of what you're doing.
08:56 You're talking about morbidity, so living better in the life that we have, living longer.
09:03 This particular drug, that's one of many, but let's talk about this drug right now.
09:07 The target market would be what, aging boomers?
09:12 Would all of it, like young people so that they can just keep their metabolism their
09:16 whole life?
09:17 Who's going to be buying this?
09:18 So the secret to Cambrian, the way we've been able to make it work as a drug development
09:25 business and not just like a supplement company or something peddling anti-aging cures, which
09:30 we do not do, is that we go through the steps regulated by the FDA and the European Medicines
09:37 Agency and all of these drug regulators to treat specific conditions.
09:43 And those specific conditions can include obesity, they can include cardiovascular disease,
09:49 metabolic disease like diabetes and kidney disease and liver disease.
09:52 These are all sort of lifestyle diseases that can be mitigated with proper exercise and
09:59 diet, but man, it's hard for most people, especially people who are already sick, to
10:03 stick to those regimens.
10:05 So that's where we will start.
10:08 And then once you've got a toehold there and you're on the market or you've really shown
10:12 that it's efficacious in people in clinical trials, then it's sort of a sky's the limit
10:17 conversation where we can identify, all right, well, who else could benefit from this drug?
10:22 Would you and I benefit from it?
10:23 Why, yes, I would.
10:25 How could we measure that, right?
10:26 And those are further clinical trials that we can do.
10:30 The thing that I love about doing drug development versus just building a company that goes and
10:34 sells stuff is that we have to justify every single claim that we make.
10:41 So if we ever say, "Oh, this is something that you and I should take," that future happens.
10:46 It will be based on large placebo-controlled, randomized clinical studies that we and our
10:52 doctors can look at and say, "Yep, that's having a real positive effect on our biology,
10:57 on our health, and then let's do it."
11:00 You know, traditionally with drug development and especially entrepreneurship, it's a two-track
11:05 system, right?
11:06 You've got the speed of policy and regulation, which is very slow, and then the speed of
11:11 technology, which especially now can be very quick.
11:15 Is that a frustration for you or are you somehow navigating the system faster than others?
11:21 I don't know if we're doing it that much faster than others.
11:24 It's certainly a slow game, right?
11:26 Developing drugs to go from the discovery, like when an idea is a twinkle in a scientist's
11:31 eye to the point that the first drug is approved is something like 15 to 20 years of work.
11:37 It is a massive time and money investment to get that way.
11:43 Luckily, we live in a system where that risk and time and entrepreneurship can be rewarded
11:49 for investors that are patient, for companies that work hard and do the best that they can
11:54 to work with regulators.
11:57 And that allows us to take these really long-term bets and have a very high bar for evidence
12:02 before we go onto the market.
12:04 Which is what big pharma, right?
12:05 Like the pipeline and make…
12:07 So is it easy to make money now or is that a sensitive topic?
12:11 Easy is a big word.
12:12 Okay.
12:13 But are you…
12:14 It is possible, what I would say.
12:15 So there are a group of specialized investors that have the long-term thinking to think
12:21 about the risks as well as the upsides for something like specialized drug development
12:27 in biotech.
12:29 The overall returns in this area are as good or better than in the tech space.
12:35 But the companies like Cambrian look very different, right?
12:38 Because they're spending lots and lots on R&D.
12:40 We don't spend anything on marketing.
12:42 We don't spend anything on like acquiring customers or Facebook ads.
12:46 All of our money is on…
12:47 No tiny purple pill ads on TV.
12:49 Exactly.
12:50 It's all research and development.
12:51 Yeah.
12:52 And it's all to generate this data in placebo-controlled trials.
12:55 And then once you've got that data, then there are long-term plans.
13:00 There's big pharma companies that you can work with.
13:03 You can work with more longer-term investors.
13:05 You can take the company public.
13:07 There's all of these other options for getting onto the market.
13:10 This drug you just mentioned.
13:11 So people are watching like, "I love it.
13:13 I want it."
13:14 Do they have to wait 20 years to get it?
13:16 Thankfully, it's not 20 anymore.
13:18 So what's the likely timeline for a drug like this?
13:20 So this is the one where I have to, again, be super careful.
13:23 A very careful caveat.
13:24 We're not sure.
13:25 This is…
13:26 But perhaps how long it will take.
13:27 So the trial that we're running now is called a Phase 1B trial.
13:31 And so this drug has been in about 150 human patients already to test, to screen for safety
13:37 and interactions with other drugs and so on.
13:40 And you're finding good results?
13:41 So far, it looks quite good.
13:44 The trial that we're doing now is the first one where we'll be testing it in pre-diabetic,
13:50 overweight and obese people to see if we can correct metabolic dysfunction, but also to
13:54 test broadly safety for people who are on it for a longer time.
13:59 After that trial, we have at least two more that we will need to run before the drug can
14:05 go on the market.
14:06 So we're talking broadly second half of the 2020s.
14:10 So we're at this dawn of…
14:11 Not even dawn, but we're in this new era of innovation with generative AI and just
14:15 a lot of the tech.
14:16 How is that impacting what you do?
14:19 Because it would seem to be able to speed up at least some of the data analysis.
14:24 That's definitely true.
14:26 And I think technology broadly, AI specifically, is impacting our business in the drug development
14:34 world at almost every level.
14:36 So Cambrian is not an AI company, but we are a technology literate company.
14:44 And that means that we incorporate AI to do optimization of drugs before we're ever
14:49 putting them into humans.
14:51 We use it to find and screen patients by finding the patients who are best fit for our clinical
14:58 trials.
14:59 We use it to identify key areas where we should kind of match the drug to a disease.
15:04 All of these tools are now available to us using these advanced computational mechanisms.
15:10 And so that's plugging in all across a very complex business.
15:14 Is the FDA or Washington, are they starting to speed up as well the way they have for
15:19 example, unique diseases, they fast track certain medications?
15:23 Will they do that for aging and obesity?
15:26 So we are just beginning to talk with our regulators about something that's not necessarily
15:35 aging.
15:37 But instead what we put under the broader banner of preventative medicine.
15:42 I think we're at the cusp of living in a world where we don't just react to disease
15:47 as a healthcare system, which is extremely expensive.
15:50 We know that like dollar for dollar the American healthcare system is worse than any other
15:53 developed economy.
15:55 And a big reason for that is that we wait for people to get sick and then try to do
15:59 something about it, which is the least cost effective way of approaching it.
16:03 So if we could use novel medical technologies to prevent people from getting sick and invest
16:09 in that systematically across FDA, but as well as Medicare and Congress and so on, there
16:16 could be a push for preventative medicine that would not just benefit folks like us
16:19 working on the biology of aging, but also vaccines and antibiotics and even behavioral
16:25 interventions, mental health interventions.
16:28 And I think that's the push that's going to define the next half of this.
16:32 I want to get back to this kid who was watching his grandfather die very painfully of cancer.
16:39 Is this the vision that, is this realizing the vision you had then or has your sort of
16:44 vision and mission changed?
16:46 It's honestly been, you know, almost a straight line approach from that point.
16:53 It's been more than 20 years now.
16:59 And when I was a teenager, I said to myself, I'm going to figure out how to build medicines
17:04 that can prevent, not just treat disease and keep people alive and happier and healthier
17:09 with their families longer.
17:12 And we're closer to that than we have ever been.
17:15 And now that those discoveries are coming into humans, it's so exciting.
17:19 Can I talk a little bit just before we end the philosophical questions around almost
17:25 culpability, like the way we sometimes pathologize lifestyle issues.
17:32 So let's take obesity.
17:33 I mean, eat less, exercise more.
17:35 We know that there are lifestyle changes that are very difficult for humans to make.
17:39 But when you give somebody a drug, sometimes it feels like it's something that's stopping
17:45 you from doing the behaviors that will make you live longer.
17:48 Will that, do you think about that?
17:50 So this is something I think actually a lot about.
17:53 And I want to maybe start by looking at the flip side of this, which is I think you can
17:59 say, "Hey, obesity is a disease."
18:01 But the flip side of that is almost like victim blaming to say, "Hey, you are obese and it
18:06 is your fault."
18:07 That's true.
18:08 Right?
18:09 Because you're not doing these things.
18:10 That happens a lot.
18:11 And so the way that I tend to look at it is that evolutionarily humans were programmed
18:16 to be lazy.
18:17 Feast and fan.
18:19 And feast as much as we could, right?
18:21 Because we didn't know when the next meal was coming.
18:23 So we would eat everything, especially sweet, tasty things loaded with calories.
18:29 And eat everything that we could.
18:31 And then we would program our bodies to not spend that energy and not want to spend that
18:35 energy if we didn't need to.
18:38 And so that's our evolutionary programming.
18:40 And so the fact that we can use modern technology now that we know for most of us that the next
18:45 meal is going to be around the corner if we want it, to be less voracious and program
18:52 our metabolism to be okay with spending energy.
18:55 I feel like you could frame this from a philosophical perspective as like updating our wet wear,
19:01 our biology to match with the modern age that we're living in.
19:05 And I think that's a more positive and future focused way of framing this.
19:10 And what we see from, for example, the obesity drugs that have come out is that when people
19:14 start losing weight, they feel better, they can move more, they have less pain.
19:19 They actually exercise more.
19:21 And I think that as we talk about other ways, maybe even ones with fewer side effects that
19:26 move forward, I expect you'll get people who will end up eating better and moving more
19:32 as a result of changing their biology to be more matched with the modern era.
19:38 That's my optimistic take.
19:39 So is there anything else on your radar right now you'd want to put on ours?
19:43 Oh, about a million things.
19:46 The last one that I would mention, which is not the drug we've been talking about, but
19:52 the best performing medicine for extending healthy lifespan in mammals, and this is in
19:58 mice where it's been shown, is a drug called rapamycin.
20:00 Rapamycin.
20:01 Yeah.
20:02 It's an FDA approved drug, but it's approved for suppressing the immune system and as a
20:07 cancer treatment and as an epilepsy treatment.
20:11 And it has a lot of side effects.
20:13 And so one of the clinical trials that we're almost ready to start is that we have the
20:18 first version of this class of drugs that rapamycin is in that seem to maintain all
20:24 of the positive effects, but have pulled out the negative effects.
20:27 So we might be able to use them safely in humans.
20:30 That's obviously a big TBD, but those human trials will start as early as next year.
20:35 It's exciting.
20:36 Very exciting.
20:37 Thank you for joining us.
20:38 I look forward to continuing the conversation.
20:39 Thanks so much for having me.
20:40 This was fun.
20:41 Great.
20:41 Thank you.
20:46 Bye.
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