Motley Fool Money - Anglerfish, Gila Monsters, and the Origin of Weight Loss Drugs

Episode Date: July 30, 2023

Weight loss drug sales are estimated to hit $44 billion by 2030. Many of these treatments can thank previously obscure research on a carnivorous deep sea fish for their development. Rolfe Winkler is a reporter for the Wall Street Journal covering digital health. Ricky Mulvey caught up with Winkler to discuss: - The origins and science behind weight loss drugs. - The challenge of selling lizard venom research to pharmaceutical companies. - What decades-old research on anglerfish reveals about modern side effects for Ozempic. - And why it’s “not too hard” to keep dozens of Gila Monsters in your basement. “Monster Diet Drugs Like Ozempic Started With Actual Monsters”: https://www.wsj.com/articles/ozempic-mounjaro-gila-monster-anglerfish-8c9c1ff2 Companies mentioned: NVO, LLY Host: Ricky Mulvey Guest: Rolfe Winkler Engineers: Tim Sparks, Heather Horton Learn more about your ad choices. Visit megaphone.fm/adchoices

This episode is brought to you by KolaGard. Do you know what's really scary? Not screening for colon cancer when you turn 45. The Koloard test is non-invasive, requires no special prep or time off work, and ships right to your door. In just three simple steps, KolaGar takes the scare out of colon cancer screening. If you're 45 or older and at average risk, ask your health care provider about the KoloGard test. Koloagard is available by prescription only. Learn more or request a prescription today at kolaGar.com slash screen. He's basically telling all these pharmaceutical executives, hey, look at what I got here. I got this peptide that actually has these great effects in diabetic mice for an extended period of time.

You should license this. And most of them said, no, what are you talking about? It's a lizard venom. I'm not going to inject that in humans. That sounds crazy. I'm Mary Long, and that's Wall Street Journal reporter, Rolf Winkler, co-author of a story titled Monster Diet Drugs like Ozepic started with actual monsters. The market possibility for these monster treats.

treatments have caught investors' attention. It's one reason why the drug makers working on these products, like Eli Lilly and Novanortisk, have outpaced the market's return by 20 percentage points over the past 12 months. But overnight sensations can take decades to create. And these blockbuster treatments trace back to previously obscure research on deep-sea fish and venomous lizards. Ricky Mulvey caught up with Winkler to discuss the science behind weight loss drugs, what the early research reveals about today's side effects, and what it's like to be bitten

by a heel a monster. Weight loss drugs, including OZempec and Wagovi, started with anglerfish and possibly venomous lizards. Rolf, I really enjoyed the story you wrote with Ben Cohen, and it enlightened me about the very strange and long path that these drugs take. It was a fun one to write. Yeah, they have a sort of interesting history. You'd think that as fast as OZempec has sort of captured the zeitgeist in the past, I don't

know, eight, nine months. You think they kind of came out of nowhere. But this class of drugs, actually, the first one was approved in 2005. And their development, science behind them, dates back to 1980. Yeah, it starts possibly with the angler fish, right? These bottom feeding fish that are known for their luminescent fin rays, which attract little tiny fish, which they then eat. But they also are able to create this hormone that shows up in the weight loss. drugs today. Can you describe how that works a little bit? Well, yeah, the connection there, anglerfish are these ugly, disgusting fish that have incredibly sharp teeth, you know, these carnivorous bottom feeders. The connection there is,

really, you may have heard of these drugs sometimes referred to as GLP1 receptor agonists. Basically, they mimic a hormone in the human body called GLP1, OZempic and what govi-do. Mujaro, the other big drug, it mimics two hormones, but GLP1 is sort of a star player here. And the anglerfish is central because it was in research on anglerfish dating back to 1980 that helped us identify this hormone. It was first identified in the anglerfish and then later in humans. And it was then, you know, they discovered that this hormone actually has what they call insulinotropic effects, which means it stimulates insulin release in the body. And the reason if they, if you want me to get into it, the reason they went with anglerfish, also a fun part of the story, back in 1980, there was this new technology called recombinant DNA.

It really launched the biotechnology revolution. It helped us create the first human synthesized human insulin, for instance. Basically, it's a, I'm going to butcher this, but it's kind of a cloning tool. Really brilliant invention back in the 70s, but people were afraid of it, as they are of many new technologies like AI. They thought that what they do in recombinant DNA is they take bacteria often and they'll splice different kinds of DNA together and then put it into bacteria that will propagate that DNA.

people worried, wait, what if this gets in the water supply? And so there were restrictions in Massachusetts where these researchers were working. You couldn't do this work on mammals. And so they decided, well, can we do it in cold-blooded animals? And they said, yeah, and they got it. They were able to do that. So they went fishing for anglerfish. They hired a guy to go catch this stuff, throw it on the dock.

And it ended up being lucky because the anglerfish actually have a special organ that produces the hormones they wanted to study, which made it easy for them to get samples of puretition. So anyway, it's kind of, that was really the science that led to the discovery of GLP1, which is the all-important hormone that we're mimicking inside today's drugs. And today's drugs sort of have somewhat solved a similar problem that the GLP1 presents, which is that it vanishes from the body quickly. And it makes people nauseous, but one of the ways they were able to delay it vanishing comes from scientists studying animal venom.

So having discovered this human hormone called GLP1, that was early 80s. Fast forward to 1986, 1987, they discovered what it did, that it had these effects that stimulated insulin release. But they also discovered that it disappears, it gets chewed up by enzymes in the body in minutes and gets washed away by the kidneys. So you can't really just inject GLP1 into humans and hope it'll be a good drug because it's just gone really instantly. To test it, just to see if it had these effects, you know, they were looking at with insulin stimulation. They were thinking, well, maybe this is good for diabetes.

They had to infuse people with an IV, like a constant drip, which is not anybody's idea of a marketable pharmaceutical, walking around with an IV pole, right? But they wanted to study it to find it had these effects. Sure enough, when you're mainlining it, if you turn up the dose, it just made people puke, which foreshadows today's side effects from these drugs. The next interesting sort of kind of side road in this whole story was another animal, Gila monsters. They're native to the American Southwest. They actually make a hormone inside their body that is similar to GLP1.

It's 50% the amino acids, the amino acid kind of structure of this hormone inside the Helomoters, 50% homologous is the word, to human GLP1. And the person who discovered this was a scientist at the Bronx Veterans Administration of all places who happened to be an expert in identifying peptides. He'd met a guy who'd done Helo Monster work dating back to 1980. And they proposed a collaboration. They identified this hormone. They put it into mice.

and they learned that, wait a minute, it actually helps the mice control their diabetes. And, crucially, it does it for 24 hours. I don't remember if it was exactly 24, but it was for many hours. And so that Bronx Veterans Administration researcher, his name was John Eng, he thought, hmm, this is interesting. I'm going to patent this. And then I'm going to try and sell it to pharmaceutical companies. And that is a long, multi-year process, and it was expensive, and he's on the road,

postering at conferences. They call it postering, because you do. some scientific research and the people who were throwing the conference, they're not going to let you give a talk on your research. What they'll do is they'll let you put up a poster in a conference hall and stand next to it. It's got to be a, you know, for him, nobody wanted to talk to him. It had to have been a pride-swallowing experience a little bit. Here he is with this poster of this work he's done with Keel Monster Venom. It was a derivative of basically their venom that, where they found this peptide. He's basically telling all these pharmaceutical executives, hey, look at what I got here.

I got this peptide that actually has these great effects in diabetic mice for an extended period of time, you should license this. And most of them said, no, what are you talking about? It's a lizard venom. I'm not going to inject that in humans. That sounds crazy. But one pharmaceutical executive at one of these conferences looks at his poster and says, huh, that's interesting.

Maybe this is the key to turning this GLP1 stuff into a drug. And so he licensed it. And then the real hard work begins. And then it's a, really, it was a nine-year process of developing it, clinical trials. And in 2005, you get a drug called bieta. The generic term is called exenotide. That was the first GLP1 receptor agonist that came out. And it was derived from the Heli Monster Venom.

And it's sort of interesting to the story of today's drugs, not because they're derived from Heli Monster Venom. Those guys, Novo Nordisk and Eli Lilly solved the problem in different ways. But what some of those folks will tell you in this world is like, look, that drug demonstrated that this could be done, that you actually could come up with a GLP1 mimicking drug that lasted in the body for a sufficient period of time that it could be sold as a drug. And so then you get the pharmaceutical companies kicking it into high gear, the research and development. development budgets, and sure enough, you get the drugs we have today, which are leading to phenomenal weight loss. So we'll give the anglerfish 100% credit in developing these drugs and perhaps the

Heel a Monster partial credit because they're not injecting the specific, the venom is not a part of the current drugs that are being made today. Correct. They actually, so Exenotide when it came out was, and by the way, all of these drugs, we really started as treatments for diabetics. That's what that started as. It had positive effects for diabetics, but you had to inject it twice a day. So it's better than an IV infusion, but it's still not, and by the way, the needle they were using for the injection was, it was this, the gauge of the needle was, was larger. It was not super comfortable. If you've used Osepic

and Wagovior Manjaro, today's drugs, I haven't, but people, who tell me, it's basically a painless needle, tiny, tiny little thing. But so, but that drug, bigger needle, twice a day, not, you're not going to get a blend. And by the way, you didn't get any kind of blockbuster weight loss out of it. So it wasn't itself going to be a blockbuster drug. But then Novo Nortis comes out with its drug called Laraglotide. Well, you know it as Victosa. That was a bigger drug. It was a once daily injection, also a smaller needle and better effects. And by the way, they showed that it had benefits, cardiovascular benefits. So one of the things that diabetics really suffer from is basically cardiovascular trouble, heart trouble.

And this drug, they demonstrated had benefit. It protected the heart as well as helping control the diabetes. But since then, it's just been a steady advance. After that, the next drug from there was Trulicity from Eli Lilly, which had similar a similar impact as laryglotide and controlling things, but it was a once-weekly injection. Then you have novo-nortis comes out, comes back with OZempic, approved in 2017, another once-weekly, which has even more benefits. And what they discovered was this incredible weight loss of an average of 15% over a period of just over a year on people who are using the drug, which is

now you're starting to talk real numbers. When you have somebody who's obese, 15% of their body weight can be a large, large number. And it's just, and there's more coming behind it that have, that show, you know, the data's even better. Promise, only one more Gila monster question, but this is a burning question I've had since reading your article. You feature a dentist, Mark Seward, because when you're studying Gila Monsters, you've got to find him. He is a dentist in Colorado Springs. And this guy has 100 Gila monsters in his basement. Did you find out why he has so many of these very specific lizards? Seward has today, that this is, by the way, when he is part of that story, that was around

2000. They were developing the drug. And really, you know what? They don't need to find Gila monsters because you can find there. You can get powdered venom to study. And you go to places like Miami Serpentarium, which that's its own interesting story, where the guy who ran that probably handled millions of snakes in his life and survived 170 poisonous snake bites. That's where they got it.

But during the course of studying it, the small company that had licensed this Heli Monster Venom did this compound to turn it into a drug. They just wanted to know more about what does this thing even do in the heli monsters, this compound? We need to study it. So how do you do that? They find this guy. He was a dentist in Colorado, whose hobby was raising heli monsters in his basement.

And he had at the time over 100, he told me. Now he's got probably over 60. He still does this. He's retired from dentistry. And it's actually not very hard to keep these, the Gila monsters because really they live most of their life below ground. They come out, they eat a few meals a year, and then they store the fat in their tails and slowly digest it.

So it's not too hard to basically keep a bunch in your basement because that's not unlike how they live in the wild anyway. So the small pharmaceutical company finds this guy who has a bunch of Gila monsters in his basement. We want to find out what this hormone is doing inside the heli monster. So we need you to do blood tests on the helen monster. So he's got him. He's, he had to, you know, feed them and then take blood, you know, stick a needle in their tail and take out blood samples at specific intervals. And, you know, he told me that in all of his years, all of his years raising helen monsters, he really does helen monster husbandry. He's really kind of just breeding them. They're an endangered species,

and he's breeding them. So he's adding to the population. Call him the Elon Musk of the Helo Monster class, right? So he had this restraint. He said in all these years, the only time he's ever been bitten by a Helo Monster was when he was doing these experiments, right? He's got one of the Helo Monsters

in one of these restraints he's built. And, you know, he's sticking the needle in the tail. And one of the Helo Monsters said, you know, and slipped its restraint, turned around and just snapped. He tapped onto his palm and he said, it's like a wasp sting, but a lot worse. Did you go to the hospital? He said, no, I had to keep doing more blood draws. And 15 minutes, so I walked over to sink and I washed it out a lot.

He didn't call a sick day after getting bitten by a Gila monster. You know, I feel better, I feel better knowing there's a conservation angle to this and that he's not just keeping dozens, if not 100, heel of monsters in his basement. He doesn't go and from the wild and bring them as far as I know. He doesn't go catch them and bring them into his house. Good. He's breeding them. Jumping to today, one of the incredible things about this drug is that, like, OZemPEC may not

just help with weight loss, but it might help with alcoholism and drug addictions because apparently it reduces the brain's reward system to dopamine. Are we seeing any of the side effect issues from the early research? Are there any clues from the early research on these weight loss drugs that are showing up today in the side effect issues besides denials? and the vomiting. Really that. I mean, the early research, well, there's a whole bunch of stuff there,

depending on what the time you got. Another fun element of the story is when they were first studying GLP1 and they were doing these IV studies where they're infusing people with various doses. There were at least two different studies where I spoke to people and they said when they turned up the dose, people just vomited. They got sick. And then they learned the way to take these drugs is to titrate. them up. You started a low dose and your system builds a tolerance and you work up to the therapeutic

dose. So that was certainly foreshadowed. There was a scare related to these drugs, circa 2009, 2010, when a couple of doctors came out really hard arguing that they caused pancreatitis. And that was something that for a time threatened the drug class. There was pressure on the FDA to pull it to pull the drugs. The FDA not only didn't pull the drugs, they in effect rescued them because there was a paper in the New England Journal of Medicine. I think this is 2015. It was 2014 or 2015. It basically said these fears about pancreatitis, we don't see it in the data. It's not there, according to the FDA. So that put out the fire, as it were. But that was, you know, when it comes to side effects, I think there's, on the one hand,

And, you know, in terms of long-term treatment, on the one hand, this drug class has been around, remember, since 2005, since that first drug, the Helomaster drug, that one came out in 2005. So you do have some long-term data on the use of these medications. At the same time, Ozympic and Wagovi and Manjaro are being used by a population of people that is so much larger than any of the other prior drugs. that there, I think scientists are on guard for, you know, are there going to be other things that pop up? Recently, the European Medical Association, God, is that what the, it's EMA. I forget what the acronym actually stands for, but their FDA has had reports of people who are having suicidal ideation, depression come in from, they say come from these drugs.

So they're investigating that. they're investigating those reports. I think that's something you'll see. Whenever you put a drug into this into so many people, you may end up seeing effects that you didn't encounter during the clinical trials. You have a larger sample base. The N is an order of magnitude larger. You know, you've got, you're talking instead of a few thousands of people that are testing these things.

We're talking millions. and, you know, people are saying that there could be tens of millions of people. If the price comes down, there's hundreds of millions of people worldwide with obesity, never mind type 2 diabetes. So this is going to be applicable to a very, very wide population of people. And the drug companies are counting on that. It would be interesting to see how this story continues to develop. The story is called Monster Diet Drugs like Ozempic.

It started with actual monsters. It's in the Wall Street Journal. Rolf, that was one of my favorite business stories I've read in a while. I appreciate your work on it and appreciate your time on Motley Fool money. Thanks, Ricky. Yeah. Happy to be here. As always, people on the program may have interests in the stocks they talk about. And the Motley Fool may have formal recommendations for or against. So don't buy ourselves stocks based solely on what you hear.

I'm Mary Long. Thanks for listening. We'll see you tomorrow.