The Great Peptide Debate with Martin Shkreli & Max Marchione

0:00John Coogan:The peptide debate. Welcome to the stream, guys. How are you? Hey, how's it going?

0:07Martin Shkreli:Thank you so much for taking the time.

0:09John Coogan:Why don't you both start with an introduction on yourself and maybe your core thesis around peptides? Martin, why don't you go first? Oh, Max. Okay, sure. Let's start with Martin.

0:22Martin Shkreli:Yeah, so I'm the pharma bro. I represent the interests and the, I don't know, I guess, viewpoint of the pharmaceutical industry, including, but not limited to Pfizer, Merck, Eli Lilly, et cetera. I'm sure those guys love that. You're the face of pharma, whether they like it or not. There you go. I'm sort of a self-trained biopharmaceutical expert. I think I can speak at a pretty high level about every inch of the pharmaceutical industry. I've discovered brand new drugs. I've acquired drugs. I've commercialized drugs. Just about anything you can do in the drug industry, I've done it. And so I'm very concerned about the peptide craze.

1:04Martin Shkreli:I think it comes mostly out of psychological issues, which we'll discuss. The need for identity, control, distrust of institutions, all kinds of things like that are leading to what we're seeing today. Great.

1:22John Coogan:And Max? Hi, I'm Max. Former peptide skeptic turned peptide believer. I run a healthcare company called Superpower. And our thesis is that the health system today does a good job when you're sick. It doesn't do a fantastic job at preventing things and actually allowing people to be their best selves. I say a former peptide skeptic because they seem scary. and I say a converted believer because I spoke to dozens of doctors and heard hundreds of clinical vignettes from people who had their lives changed. Now, I don't believe all peptides are safe. I do believe we need more research. But I think there are a subset of things that have improved people's lives.

2:08I also think as a modality, peptides are one that are more interesting than before, now that injecting is normal. Now the wellness and optimization is normal, not just treating disease and now that we have AI for things like computational discovery. So we're early, we need more research, but I think peptides are exciting.

2:28John Coogan:Martin, I'll let you just respond. Yes, it seems like you're ready to go. But it would be useful to at least define the conversation a little bit more because when we say peptides, we could mean Ozempic prescribed by a doctor for someone who has diabetes and is very overweight. It could also mean the Wolverine stack taken by a 15-year-old in a gym in Miami, right? And like, there's a wide gap here. So let's maybe narrow it down a little bit to probably off-label use. I don't know exactly where things start to get fuzzy for you guys, but defining a little bit more of where the actual point of debate, because I imagine that there's agreement with the extremes.

3:13Martin Shkreli:Yeah, I mean, isn't there a problem when we have to redefine semantics that have been defined forever? Isn't this like somebody saying, you know, I'm using, you know, GPT instead of using AI or something like that? Like, there's a specific meaning, like peptide has this very specific meaning, and they're not new. They're 80 years old, people have been using peptides forever. And in fact, in pharma, you try to avoid peptides because of their inherent weaknesses. You go for small molecules or really large molecules like antibodies. Peptides are sort of the worst of both worlds. So the idea that we've taken this kind of like last place drug class and then turn that into like the standard bearer for do-it-yourself medicine is kind of humorous to anybody who actually understands pharma.

4:00Except that the last drug class has the potentially most impactful drug of all time, or set of drugs of all time, the GLP-1 receptor agonists. So I'm not saying we only have peptides in the toolkit. I'm saying the genie's out of the bottle and we cannot ignore peptides as a tool in the toolkit. Small molecules, just framing it for people who don't understand the difference between these things, small molecules are made synthetically. Peptides tend to be derived from what already is happening in the body. right dna is the building block of the body and encodes for rna which produces proteins and peptides so these peptides naturally occur now it can sometimes be hard to patent a naturally occurring thing you can but it's a little bit harder small molecules on the other hand are things that humans design to block biology to block typically block something that is happening in the body and again i'm not saying small molecules are bad but they're they're kind of the two different modalities we're talking about here and we've seen one category of peptides glp1 already changed the world.

4:58And my contention is that there are other categories of peptides that are under-researched but have really interesting kind of clinical vignettes that might change the world going forward. Martin? But I think like why we're having this conversation is because people are just, you know, injecting a number of them into themselves now. And you're saying they might change the world, but people are going through the process of self-experimentation and there's a bunch of companies, private companies, that are happily facilitating this and profiting off of it when it seems to be a large number of risks that are still unknown.

5:37At least that's my point of view. Yeah, exactly. Yeah, I think that's right.

5:44John Coogan:So maybe let's start with stuff that's not fully FDA approved. I think the canonical example would be like the Chinese peptides, the retas, the stuff you buy online and inject, and it's based on some interesting scientific literature, but it hasn't actually been through the full FDA process yet. Where do both of you stand on that?

6:07Martin Shkreli:Yeah, I mean, why do you have a right to pirate somebody's intellectual property? You know, this is the property of Eli Lilly. They discovered it. They spent billions of dollars on it. You want to steal it? You want to work with a Chinese company stealing it. I mean, that's not good for America. That's not good for the drug industry. And guess where do these drugs come from? They come from American R &D labs. And if you keep stealing them and pirating them in this weird twilight DIY drug system, which is not very large, at least compared to pharma, I don't know if you make a big impact, but if it went very large scale, you would.

6:44Martin Shkreli:I mean, you'd stop having drugs the same way pirating music would have huge ramifications for the music ecosystem. So you have to respect intellectual property to some extent. And then taking a redditrutide, which is just sort of a GLP plus, if you will, instead of just waiting for it to be FDA approved or using Ozempic, I think this is the worst risk-reward decision you could possibly make. It's like some of the decisions I used to make in the past. What is your upside to taking illegally manufactured redditrutide from some other place and you can't verify it, etc., versus just taking those Mpik.

7:23Martin Shkreli:The people that take peptides and have these peptide stacks are mostly people in SF, maybe New York, they're very wealthy people, they don't know what the rest of the world looks like, nobody else in middle America is excited to do this, it's not normal, Max, to inject yourself with things, you know, this isn't like a thing everyone should be doing. And so, to me, the retitrutide case is really insane because this is a drug that Eli Lilly is going to get approved eventually. And the fact that there are people dying of certain terrible diseases and they need compassionate use. They need to get on extension programs, but nobody needs retitrutide now, right now before FDA approval in a few months.

8:04Martin Shkreli:I think we agree on this. So I think the things we agree on are that the existing FDA approved GLP-1 receptor agonists are an interesting category of drug and they're a peptide and they're impactful. I think we also agree that companies should not do things illegally and infringed on the patent for retta right i do think the patent system incentivizes innovation i think the crux of where we disagree is not and just quickly on the this is the nsf thing that is not true if you speak i know dozens of people who own these research use companies and if you speak to them the majority of their audience is middle america not no not sf tech bros despite the tech bros being noisy on twitter i think the crux of where we probably disagree is the 14 or so peptides that rfk has said they might move from category one two meaning they cannot be compounded back to category one meaning they can be compounded and i guess my like general statement here um is that uh people are taking these compounds right they're already using them at scale right and the way to minimize risk the way to minimize risk is to move them from category two to category one right to legalize them because the risky thing is the dodgy supply chain we have today the risky thing isn't the isn't the risk isn't isn't the risky thing just doing like massive sort of unofficial you know human trials when we don't know i don't think so so i think i think that is true um for peptides that we do not have longitudinal clinical experience and patient experience with but let's take something like bpc157 which is one of the most controversial ones so let's let's go right to the meat of things let's take something like bbc 157 my contention is that thousands of doctors prescribe this they do and have prescribed this you can't prescribe this drug uh they give it to their patients right you can prescribe the semantics give it to their patients it's not a drug thousands do that my statement is not the semantics of prescribing my statement is thousands do this okay my other statement is that millions of patients have taken this at least hundreds of thousands i believe millions have taken this.

10:09That clinical experience, again, is not an RCT, but we cannot ignore it. Yes, you can.

10:15Martin Shkreli:Yes, you can.

10:16John Coogan:Wait, wait, wait. It sounds like there's some sort of fundamental disagreement here about the way BPC-157 is being distributed right now, because I know people that have told me that they've taken it. I thought that they were getting it prescribed or recommended to them. Martin, what is your... We can agree that it's being given to them. I think they're getting it, but what's actually happening here? How is this happening? Out in the back alley. Is that what's happening? They meet in the back alley. It doesn't seem like that. It seems like there are doctors that do have the ability to. There are many of the best doctors in the world.

10:50So when I was first introduced to peptides, one of the most esteemed doctors in the U.S. said to me, Max, you take so many supplements. Have you explored peptides? Because I think they're a really interesting modality with a few decades of clinical use. Sure. Right? And when he said that to me, I was like, no way. This is bullshit. I'm not injecting myself with something that was weird. So what I did is I went around to around 20 different doctors whose opinions I respect.

11:15And I asked them about peptides. And normally when you ask these doctors about anything, you ask them about red meat, you're asking about spinach, they're all divided. They're all like one view, another view, punches with peptides. Just about all of them except one said these are really interesting. I have used these in my patients. I believe the endogenous molecules, peptides that exist in our body, are going to be the future of medicine. And those doctors have the incentive to not be wrong. If they're wrong, they could go to jail. If they're wrong, they can have their license stripped. If they're wrong, patients don't come back to them.

11:46So they have the maximum incentive. And for 10 to 20 years, they still give this to their patients. And their patients say, my life changed. Now, you might say it's placebo. My statement is the patient says their life changes and the doctor sees that.

11:58John Coogan:Okay, Martin, I want you to react, but I also want you to sort of set aside the intellectual property argument. I like that argument, but let's focus on what doctors are doing, how BPCY157 is being delivered, that type of thing.

12:11Martin Shkreli:So I'm a drug hunter, right? People like me, Vivek Ramaswamy, we look all around the world for medicine to buy and medicine to put into companies that great firms like A16Z and Founders Fund and other more healthcare maybe focused firms will fund, take it to the IPO, which I've done before, and get paid huge amounts of money. That's what I do. That's what I'm good at. That's why I'm the pharma bro. BPC-157 is the biggest scam I've ever seen. It does absolutely nothing. There's no redeemable value to this. Do you know the story about it? Do you guys know, Jordi? No, please tell us. This guy in Croatia made it, Sijic, my hinterland brother.

12:49Martin Shkreli:And, you know, the only publications about this drug are by him. Nobody else has published about this drug. It's not a drug, in fact. Nobody's even confirmed that it's a peptide from the gastric juice, as he claimed. Nobody can find a sequence that matches that, and the gastric juice of human beings has been thoroughly profiled. It's a 15-mer peptide, so it's 15 amino acids. Half-life is minutes. There's no plausible physiological basis for it to work, and it's been in clinical trials. Pleva was a local drug company in the Balkans. Very well-respected, might I add. And we've actually licensed BPC and tried to do clinical trials for it.

13:29Martin Shkreli:And guess what? They failed. So this weird, I want to be a doctor too thing is... Of course.

13:36John Coogan:Do you think it's placebo effect? Because, yeah, I've talked to people that say it's good for recovery. And I can imagine if you're sticking yourself with something, you might feel like, ah, I'm less sore today because it's just...

13:45Martin Shkreli:While you are recovering, you think that the drug is helping you. And of course it isn't. It's the recovery process you're going through. And there's an app for this. If you want to make real money, go make BPC in CGMP conditions and go do a clinical trial. And you can be a trillion-dollar company like Eli Lilly. Instead, you can putz around buying fake Chinese stuff and then injecting yourself and dreaming that you're doing well. I have a drug here that if I take might also aid my recovery. No, no, no, no. Should I try this? Should I tell you that it worked for me? It's an N of one. Oh, my God.

14:19Martin Shkreli:I did so great with this N of one. you know, it healed my recovery. Like this is nonsense. This is not science. Science is controlled experiments that are well done, very carefully documented and so forth. Why are we going backwards? Why do we go forwards in civilization and society? What is this urge by the valley? And I blame the valley to go backwards in time and space. I hear of you and I think other people will have it. And we don't know whether these are placebo or not yet. We can't make a definitive statement. And we don't have the RCTs. But I thought you said there was studies done on BBC 157.

14:58No, there are no human studies done.

15:01Martin Shkreli:There was one done by Pleva and it failed. There are dozens of studies of drugs that become commercialized that previously failed. Anyway, my view is we don't know whether it's placebo or not yet. That is true. And some people will say it's placebo, some will say it's not. My statement is really simple, which is you can have Martin's view, or you can have the view of thousands of doctors who have used this for 10 to 20 years and have their license on the line. The view of millions of patients who talk about their lives changing. You can have that view. My dad's visiting from Australia and he's been taking painkillers for the past four months and can't walk upstairs because his back is bad.

15:35Martin Shkreli:He took BBC 157 for three days and he said to me, Max, this is the first time in four months I haven't taken a painkiller again i'm not saying this isn't placebo i'm saying we don't know what i'm saying is i am god i'm really happy my dad's not in a painkiller yeah right my co-founder he lost three organs in hospital he had an autoimmune disease they put him in biologics he took bpc 157 he's off biologics and he doesn't have an autoimmune disease anymore again we need the study we will put our money and fund the studies put your money where your mouth is exactly but we can't ignore the real world evidence again you are ignoring it if you're not putting your money where your mouth is.

16:10Martin Shkreli:If you believe that's true. No, we are. No, no, no. Do a clinical trial. We are. Tell me about it. We're in the process of chatting with the people required to set up a clinical trial for this because we will put our money where our mouth is because I've seen thousands of doctors, millions of patients, and even the FDA, right? Who has said they're going to start legalizing, even the FDA. Okay. But Max, you can have your view and I don't, that's okay. People will have that view. I will have an opposite view and I'll put my money where my mouth is. Max, you've never done a clinical trial before, right?

16:40Martin Shkreli:You've never invested in drug companies before, but you want to do your first clinical trial on this drug, which you did in an event. You know, you've heard anecdotal evidence about. Why? Because I have seen thousands of doctors, millions of patients over one to two decades. All right. Go say to my friend, go back on biologics. Go back to hospital. Lose another organ. Go say to my dad, go back on painkillers every single day. I don't want my dad on painkillers every single day. Now, you might say that's placebo. I say I don't know. But I say with the evidence that we currently have, I believe there is more to support.

17:16You should see what this galaxy gas does for me. It's amazing.

17:21John Coogan:It's really good. No, but what's your question? Is your question, Martin, more that like, okay, you take... No pharma guy in their right mind would do this. Well, hold on, hold on. So no pharma guy would do it. Max clearly believes in this. And what is the intersection of these two things? Is it possible to do the type of study that you're talking about with Silicon Valley backing? Is a$30 million Series A enough to get started? Or do you need to go to Wall Street, IPO, do the biotech thing?

17:53Martin Shkreli:Plenty of private companies do this. There's hundreds, if not, actually, I would say there's thousands of private biotechs. Generally, they would pass on something like this. Well, yeah, so there's this body of anecdotal evidence. Yeah, unpublished evidence. Yeah, yeah, yeah. So certainly a drug hunter would have looked at this already, right? Martin, is your statement the only admissible evidence is an RCT? Yes. And what about all of the examples of when something works? Before anything works with an RCT, there's a time when it works pre-RCT. do you deny that in animals uh no in humans there are times in animals before there's an rct yes it does happen sometimes yes yes they're intelligently because they're intelligently designed drugs that were designed to do a specific thing and they do the specific thing and then they work yep this is not that and you think your statement your singular statement of placebo outweighs the again we don't know but i'm saying on the facts we have today there is more to support the fact this is more likely than not placebo than the alternative.

19:04Martin Shkreli:I would bet anything. I would bet anything. No trial of BPC would work. Okay. I guess we'll see. What else? So Max, is superpower facilitating people getting BPC-157 today? No, we won't sell anything that is not legal to compound, but I believe the FDA will make it legal to compound soon and then we'll sell it. And I believe the FDA should make it legal to compound because the genie's out of the bottle. People have seen their lives changed and they're getting it anyway. What else are you excited about? Because when people say peptides with an S, so BBB157. Thimosin Alpha 1 is fascinating. It proves in 35 countries.

19:47I take and I never get sick. I used to get sick four or five times a year. I had the most elaborate immune stacks. None of those elaborate immune stacks, the hundred things placeboed me. Thimosin Alpha 1, everyone around me had COVID a few months back. and I didn't get it. A bunch of people around me had influenza. I didn't get it. Every time I get a sore throat, I take BBC1-5-1, and the sore throat disappears. Now, this is a drug that is approved in 35 countries, right? Has some human data. Now, pharma in the US hasn't brought it through trials because they can't patent something that existed for several years.