[Music] Welcome to this week's episode of The Read Out Loud, a weekly biotech podcast from STAT. I'm Alice in DeAngeloos. I'm Adam Forrestine. And I'm Elaine Trunn. It's Thursday, June 11th, and on this week's episode, we're going to talk about one of the hottest topics in medication, peptides. More specifically, a peptide that supporters believe has powerful healing effects and is set to be discussed by an FDA advisory committee next month. Alice and I want to know what your peptide stack. We'll get into that these days. But first, a recap of this week's news and a word from our sponsor. [Music] I'm Golly Alevi, SVP of Development at Kite, a Gilead company. A Gilead in Kite, our working oncology, starts with a very simple question. How do we make progress truly meaningful for patients? Since 2020, our therapy has been used to treat more than 75,000 people worldwide, with metastatic, triple negative, and HR positive, her two negative breast cancer. We bring that same patient first mindset to other areas of high-on-met need, including CAR T-cell therapy for people with difficulty to treat blood cancers. To date, over 34,000 patients around the world have been treated with CAR T-cell therapies from our portfolio. Across oncology, this perspective guides how we design clinical trials and pursue innovation, so patients can access potential advances throughout their treatment journey. Learn more at gilead.com. Okay, folks, another week, another medical conference. Elaine was closely tracking ADA this last weekend, where we got a slew of data on all of the obesity, drug, and development. Elaine, give us the top line. What was the conference tenor? Yeah, I think thinking about how to recap the conference, we could discuss it in some different themes, and to start, is this question that we've brought up a lot on the podcast is, can we actually beat the current obesity drugs we already have on the market? Like, what if we already have the best ones on the market? Somebody raised that question back in the fall of K-84. Adam referencing himself. This is a lane. Let's carry on, sans Adam. I'm sorry, I interrupted. I apologize. Okay, so yes, we got some new data, but again, is it actually better than what we already have? We got some new data from the Metsera drug that Pfizer now has. It's supposed to be a monthly GLP-1 drug. It does show potential for monthly efficacy, but the efficacy so far doesn't look as good as what we already get with that bound. Also, they had patients start off on weekly doses and then transition into monthly doses, and when you transitioned into monthly doses, you up the dose pretty significantly, and so we saw tolerability issues as expected. We saw non-java-mitting. So, currently it looks like the Metsera data is perhaps kind of underwhelming. We have a GLP-1 glucagon dual agonist from Boeing or Ingolheim. That one also, not amazing efficacy, also very high discontinuation rates. We got a small molecule GLP-1 from AstraZeneca. That one the efficacy does look promising, but it's still pretty early. It's just in phase two, so by the time it potentially even gets on the market, Lilian, Novos, GLP-1 pill would have been presumably already be in widespread use. So yeah, I think it's like a pretty high bar for any of these drugs and development to have to clear to really be competitive on the market. So, like obviously Eli Lilly had a presence at ADA this year, and a lot of the focus was on their, I guess it's their triple G, they call it drug, the Retrotruth Tide. I'm probably mispronouncing that as I always do, but it seems that if we are going to get a quote-unquote better obesity drug, a lot of folks believe that Retrotruthide is that drug. I don't know, your thoughts on that and what did the data that was presented at ADA this year look like? Yeah, I mean, I do think a lot of doctors are excited about the Retrotruthide data. We already know it's a very powerful drug. It can lead people to lose a lot of weight very quickly. The new data also showed, additionally showed it helps with sleep apnea, with knee osteoarthritis, with cardiac measures like blood pressure lipids and things like that. So, that all looked very good. So, I do think a lot of people probably think this could be best in class. I think there are still some doctors that also I think have some reservations around the tolerability, and because it's so powerful, it does still lead to high rates of vomiting, nausea, discontinuations. And then there's a question of, this is what the data looks like in the trial. What is it going to look like in a real world? Because there is concern that if you have such a powerful drug and you just kind of unleash it into the real world, that could be potentially dangerous, especially for people who, for the vast majority of people who fall into this category of obese and overweight, they don't need that much weight loss. There was a media call that Lily Helds and Lily people were asked, you know, given how powerful this drug is, should it be restricted to use in doctors' offices to in-person doctors who can better monitor patients? Because we know that so many patients are getting it over telehealth now, it's harder to monitor them over telehealth. And the least head of cardiometabolic health basically said, "I don't know why we would want to restrict this to any one group of patients." So, it does seem like the intention would be to release it widely as how the other current obesity drugs in the market are released. Lily is person said, you know, even the lowest dose of redd is effective. But, you know, when you're getting these drugs online with little oversight, I'm just wondering, will people actually just stay on the lowest dose? I do think people are very motivated to just lose as much weight as quickly as they can. So, I am concerned about whether people will know when to stop and the safety when you just unleash it to the whole public. Redditrutide aside, like, jumping back to the earlier point, Elaine, it feels like the data that you were listing out from Metzera, from Beringer, from AstraZeneca really kind of underlines this qualm that I think you and I and Adam have had for the last year or two of, is there really that much room for growth in this market? And we really going to end up in a situation where, you know, companies are just kind of like continually topping each other that there's so much more to dig into. I look at all of this data and we're talking about these very, you know, small differences between efficacy and like, yes, there's some dosing strategy differences. But, if these drugs make it out into the mass market, are patients really going to care about that? Are they really going to be doing the research to say, like, well, this one, you know, there's like a one or two percent greater, you know, proven weight loss effect than this other compound? I don't think so. Redditrutide might be an outlier because it's so powerful. But as a whole, I kind of feel like the obesity field has lost a lot of luster. Yeah, I would agree. I think that when we're talking about this efficacy versus that efficacy, it's like, okay, how much difference are we really talking about here? I do think a lot of it will ultimately come down to the commercialization rather than the data in terms of how companies price their drugs. I think a lot of people mention like, you know, in the long run, it's going to be about volume. I think it's fair. And what about Amelun? I don't know if there was a lot of data on the Amelun drugs this year, but if I remember correctly, it's kind of a hot topic because it might be like the kindler, more gentle way of losing weight loss. Yeah, so there was data on drugs we already know. There's Cagri Sama, which is a combination of Amelun and GLP1. It's drug from Novonortiske. There is an Amelun drug from Zealand pharma. So the theory is that targeting Amelun could be a more tolerable mechanism than GLP1. I think the issue is that a lot of companies are like, okay, we still want high efficacy. So we're going to combine Amelun with GLP1. And then so you still get the same tolerability issues. So I don't know. We still need more data to know if Amelun really will be a more attractive mechanism. And this goes back to like in the real world. I wonder again, will patients care about the tolerability data? Are they going to actually look at, okay, this drug looks more tolerable than this? I do think everything is so weight loss focused. Like we always talk about how much weight loss does this lead to the, that's what the companies talk about. That's what investors talk about. That's kind of what everyone is so hyper focused on that I think that that's what patients are still focused on. Whether that really should be the focus is a whole other question, but I don't know if patients are really going to be thinking about like this tolerability of of this drug versus another drug. - I don't know, I kinda disagree on that.
point Elaine, I think that tolerability could be a differentiator because I feel like we've all known people or have heard of people who have tried the current slate of GLP ones and just couldn't handle the nausea of the vomiting and everything that can kind of come along with them. If we have a drug that really has, if it has a similar, a fairly close level of efficacy to what's already on the market, but hat is much easier to kind of stomach or to no pun intended is much easier to tolerate, I think that that could be a marketing differentiator because most people, like most average citizens, don't really know the difference of like what is 22% of my body weight versus what is 21% of my body weight, but they know like man, this drug really made me feel terrible versus this one didn't. I mean that's fair, I do think though like some law in advocacy would have to be a pretty big difference from the existing drugs we have. Yeah, you know, like it would have to be pretty significantly different for it to be a differentiating factor on the market. So last topic I want to bring up with respect to ADA Elaine is placebo controlled clinical trials. So all the studies that we're talking about, the drugs we're talking about being developed, you know, they're running these against placebo, but we're starting to see really high discontinuation rates in the placebo arms of these studies and that makes sense, right? People obviously know pretty quickly whether they're taking an active drug or they're in a control or the placebo arm. Is it time for us to stop, I say us like the industry to stop using a placebo in these studies? I would say this has been a problem for a while now, like Alice and I have been talking to people who help run clinical trials for obesity drugs and like two years ago, they were already talking about this. So this has been a kind of longstanding issue because we have these powerful drugs in the market now. If you're in a placebo group, you're like, why would I want to stay in the study when I can just go out and buy a drug? So I think there is a lot of talk about, you know, instead of placebo, the control arm should be just the drugs on the market currently. I think it makes sense because, you know, you want to maintain a good amount of people in the control arm. Whether companies would want to do that, I don't know because sometimes like we have just discussed some of these newer drugs and development may not actually look that much more competitive than the drugs we already have. So I don't know how willing the companies would want to do this. Yeah, generally speaking, when you think about any kind of drug development topic or, you know, in any disease, you know, doing, running a study with an active, an active drug and a control arm can be tricky, right? You oftentimes have to have a lot more patience to tease out differences between an experimental drug and an active drug. You know, the statistics can be different. Are you testing for non-inferiority? But like even to your point that you made Allison about, you know, how important weight loss versus side effects are, these kind of the studies, if we did run, let's say like a triple G retrochutide versus, you know, kind of a zepbound, you might start to see differences and, you know, kind of a real, more real world-ish differences in weight loss and tolerability, you know, vomiting, you know, all the sort of GI side effects. And I think that would really start to better inform and better characterize what these drugs actually are doing. Okay, so in other news this week, we got a very large biotech IPO. Allison, tell us more about that. Yeah, we got a new record, parabolas medicines raised $670 million in its IPO, really shooting past Moderna, which used to be the record holder in the pre-pandemic days. And they also raised an additional $75 million in a private stock sale to Regeneron. It's a big move for this company. This, I've spoken to CEO Matai Maman a couple of times over the years, most recently sat down with him at, you know, caught up with him around JP Morgan. And he's been really careful about the idea of when to take the company public. When he first came onto the company, he was really reticent. He was warming up to it in, you know, at the start of this year. And now they have really been very well received by the market. I also got to, got to throw out that this is another, you know, feather in the cap for Greg Verdine, who founded parabolas medicines, which was originally known as fog pharma, and also was involved in the company warp drive bio that was acquired by revolution medicines, which obviously had great data earlier this year. So good for Greg. Congrats. I do find it funny that in biotech, you know, an almost $700 million IPO is a record set on. And then we're going to have SpaceX coming out with, you know, raising like $75 billion. So, you know, puts it all into perspective. Baby steps, baby steps. Yeah, we can't, it'll be really cool when we get the first billion dollar biotech IPO. Adam, why don't you close out by telling us about the MNA that we saw this week? Yeah, GSK buying new valent, uh, developer of genetically targeted cancer drugs for $10.6 billion. Uh, you know, the same themes that we've talked about, about MNA biotech pharma MNA in this entire year, last year, all still in play here, you know, GSK looking to expand its, its oncology platform, uh, finding sources of those drugs in the biotech world. So, you know, more of the same. What do the MAHA movement and bodybuilding forums on Reddit have in common? Well, they're both fascinated by peptides. These compounds have become a hot topic of late, and there's even debate around how they should be used, and if the evidence is strong enough to allow open access to them in the United States. Undark reporter Sarah Talpus has been digging into one peptide that is the center of this conversation, dubbed BPC157. This peptide has a fascinating history and could become a more mainstream topic next month when an FDA advisory committee meets to discuss opening up access to it. In two articles written for Undark and co-published in stat, Talpus dives into the Croatian scientist that has spent decades developing what he believes is a powerful healing peptide. The gray market around them and this regulatory debate. She joins us now to discuss all of that and more. Sarah, welcome to the podcast. Thank you. It's great to be here. Sarah, you've spent a pretty good chunk of this year digging into the world of off-market and experimental peptides. Take us into this world. Who's driving this conversation and why has it grown in recent years? Yeah. That's a great question who's driving it. Initially, this all started out in a lab in Croatia and sometime around 2010, the bodybuilding community started reading these papers coming out of the lab and they then started ordering the peptide directly from Chinese factories. So, from there, it sort of grew through word of mouth. This is my understanding to biohackers and people who had unmet medical needs and eventually started getting promoted on these big podcasts, notably Jerogen, Andrew Huberman and caught the attention of people who are now key figures in the MAHA movement. So, Sarah, you're reporting zeroed in on one peptide in particular called BPC157, which was developed by a Croatian scientist, Professor Sakurich. How did this compound come to be? Why has Sakurich been so dogged over the decades that it could be an all-purpose healing tool? I would say the reason for that is that he started out with a theory, which was that the stomach is the subject of the stress response. There was a scientist named Hans Seie, who in I think 1930s published this landmark paper that was looking at how the body, this was in rodents, but subsequently translated to humans, how the body responds to stress. And one of his findings was that it seems that stress damages the lining of the stomach. And so, Professor Sakurich's theory was that the stomach must produce a substance that counteracts that stress response and returns the body to homeostasis. And the idea was that this wouldn't just act on the stomach, but that it would act on any organ. And so, he started with this theory and subsequently did studies, mostly in rodents, showing that it does seem to have effects beyond just the stomach. So, sorry, you went to Croatia to meet with Professor Sakurich and his team at his last.
You spent a lot of time but they've talked to him a lot. And I'm just curious, like, you know, you tell one of the stories you tell, and there is this great story about, you know, collecting stomach juices to sort of, to search for these kind of compounds. And ultimately, that's kind of where BPC 157 came out of, what do they say about this peptide, about what it can do, what it can't do, and kind of the scientific evidence that they've collected about this compound that has gotten so much attention these days? Yes. So they have investigated the BPC 157's effects on an array of organ systems. And what they are finding in studies, mostly in rats in their laboratory, is that it does seem to have effects on everything from, you know, blood clotting to tissue regeneration, to stomach, you know, that it can help prevent the lining of the stomach from being damaged by various, noxious agents. So, you know, I think their lines of investigation have been very, very broad, and their findings have been pretty consistent that the substance is helping and that it causes few with any side effects. So it did also track down some clinical trials that security and his collaborators have run on the compound in humans, and also learned that at one point, you know, BPC 157 was actually put in front of Blacksosmith Klein. What kind of data or clarity have we gotten about the peptides effect in humans? Yeah, this is probably the area of sort of greatest, I would say, weakness or ambiguity, in part because a pharmaceutical company in Croatia called PLEVA, they ran a phase one and a phase two trial testing BPC 157 as a treatment for ulcerative colitis in the early 2000s. The issue is that those were never published, the results were never published as full papers. They did appear as abstracts, and it was found to be safe when administered as an NMF or the given duration in this trial, but it didn't have a statistically significant effect in the phase two trial per the published abstract. So from there, well, okay, this is a long and complicated story, but the research and development arm of PLEVA went to Blacksosmith Klein. So at that point, the patenting licensing agreement went to GSK and they decided to shelve the project. In my reporting, what I found was that this was not because the substance was found to be unsafe or because it was definitively determined not to work for anything, but rather it was more of a portfolio decision and Blacksosmith Klein had other projects that they were pursuing. How did that come across to Securich and his team? What are their thoughts about how the pharmaceutical industry has approached or has handled BPC 157? Securich was very upset. I can say that. I think he thinks in his view that it's obvious that they made the wrong choice. And he has gone on since then to sort of pursue clinical trials through one of his own much smaller companies with the hope that they can eventually bring the substance to market. And I just want to go back and emphasize a point about the findings that they found. It's mostly been just in animals. There's been very few studies actually in humans. We have very little data on the effects on humans, right? That's correct. Yes. Okay, so we don't have that much data on humans. We've talked to also a lot of other experts, independent experts, about this peptide. What do they think about the data? I would say that they were skeptical. The way that this substance has proceeded as it's been researched is quite different from what peptide research typically looks like. And my understanding of how it would typically proceed would be trying to identify the receptor that the peptide acts upon looking into what is the peptide's 3D structure, trying to identify the gene that encodes it. And this has not been the focus of the curation team. They have really been focused on trying to pinpoint the effects of the substance. And again, mostly in rodents. So I did encounter a lot of skepticism. And I would also say a level of confusion about how this peptide is working in the body. And that kind of skepticism is why this is so controversial, right? Sorry. That they can't identify or anyone can prove that this is the substance that actually comes from the body that it acts on a specific receptor that has a specific structure mechanism that it's difficult to evaluate it. Is that part of the controversy? That is definitely part of the controversy. And I should say it's interesting to me. I'm not sure that they can't identify it. So much as it's unclear to me that anybody has tried to really find a receptor. This was one of the things that Sandor Zabo, whose researcher here in the United States and you've served a long time colleague of Professor Securities, said is that he would really like to see some research done trying to pinpoint some of these things. He does think that the substance is probably acting on certain kinds of receptors. This isn't in my article. I need to go back and see which ones specifically. But he was at least a big proponent of trying to test this and see if it is acting on these receptors. With all of the evidence that has been gathered and these questions still floating around, there is a debate that is happening around how much people should be able to access BPC157. You do a great job in your articles kind of describing the gray market of how people order these peptides as basically research chemicals because you can't in the United States legally sell them as human therapies. But more recently, Robert F. Kennedy and the Maha movement have kind of shown an interest in this peptide. And Kennedy has taken a stance as head of HHS that it's not the government's job to block access to unproven treatments and that individuals should be able to educate themselves and make an informed decision. Where is the debate nowadays around BPC157 and how much access people should have to it? Yeah, that's a great question. I think that there are different sets of stakeholders. And I can try to break them down. Then you've got peptide researchers. And they are saying we should not be jumping ahead of things and skipping the clinical trial process because it is crucial one of the things that these phase one, phase two, phase three trials help us understand are what are the best doses for humans? This is really the chance to kind of deep dive and get a better sense of how these drugs are moving through the body and how they're being metabolized. Of course, you can do some of this in rodents, but really they want to see this done in humans. I would say also positions at academic institutions, they want to be following evidence based medicine. They want to ensure that they have as much information as possible when they're recommending a drug medication to their patients. And so these are all people who are very strong supporters of the FDA's process and letting it play out. There are also a lot of people on Reddit. I don't know how many. I'm not sure that polling has ever been done, but they are a lot of them are on Reddit online who will give you what I think are, you know, compelling reasons why they want access to these peptides, even though they haven't been approved. For my first article, I interviewed one person who actually two people who suffered from chronic pain and they really were not well served by traditional medications that had been approved. They kind of tried everything and for them taking something like BPC157 was a smaller risk than continuing with the status quo for themselves. So I think that that is sort of there is a group of stakeholders who believe strongly that they should have access, they should be able to make some of these decisions themselves. There is also another group and I hesitate to sort of say exactly who they are, but there is an argument that's been raised recently, particularly by Secretary Kennedy, that these substances should not actually even be regulated as drugs that they are closer to supplements. That is a tricky argument, I think.
Some people would disagree with that. I think it's possible that there's some gray area, but this is another sort of question, I guess, for the future. - Another complication in all of this debate is that, as you report, there are a decent number of people advocating for the peptide, advocating for more open access to them who financially could benefit from more people using this peptide or just peptides in general, right? - There are definitely, and I would say, figures in the Maha movement who will stand to benefit from loosening of restrictions on peptides. In my first article, I specifically mentioned Gary Breka who markets the peptide on his website. Well, he markets VPC157, and I can't remember if there are other peptides up there, but that is one of them. And I would say anybody who owns a compounding pharmacy, for example, may stand to benefit from the loosening of restrictions. Last November at the Maha Summit, there was a whole panel on compounding pharmacies. There is definitely money to be made here, and I do think that it is important to look at that, particularly in an environment where there is so much hype around the peptides. - So as we mentioned earlier, the FDA's pharmacy compounding advisory committee is gonna be meeting next month to discuss whether pharmacies should be allowed to compound and then sell a handful of these peptides, including VPC157. Sorry, what sense do you have about what the experts and the advisors who are gonna be speaking, debating this issue at this advisory committee? What's that going to look like? And what do you think they might ultimately decide? - I wish that I could answer that question for you. At the moment that committee has several vacancies, I think I looked at one point and saw that the advisory committee was half empty. My understanding is that several of the committee members were let go in 2025, and that they are now looking for replacements. But at the moment, I don't think the committee has a chair, and as I said, there are other seats vacant as well. So it's unclear to me who is going to be evaluating these peptides in late July. - We've seen this issue come up with other advisory committee meetings, both at the FDA and other health agencies, and RFK Junior has played an active role in nominating and placing people on these meetings. Is that something that you think might happen here? - I am going to resist speculating on that. (laughing) - We love speculation on this podcast. - This is the speculation podcast. (laughing) - I am not going to speculate, but obviously he is the health secretary, and so it's possible. - But it does bring up the issue, right? It's an interesting thing to ponder because he has been generally supportive of peptides, as you mentioned, particularly kind of thinking of them as supplements, and perhaps these are substances that should not have to be regulated the way drugs normally are. So you would think that the advisory committee that will review these peptides are going to have people who sort of share that point of view. - I'm hearing the voice of my editor in the back of my head right now, say, "Don't speculate." - See, you're being a true objective journalist. We love that. - I can see you. - Here on this podcast, we love to speculate and go off the rails sometimes. So I totally respect your ability to stay true to the reporting that you've done. - As I'm sure does your editor. Michael, if you're listening, that's for you. - Okay, Sarah, well, while we wait to see what happens with the advisory committee meeting next month, tell us what's happening in the clinical trial landscape for BPC157. Are there any trials that are running right now that could help us answer if this peptide is doing anything and if so, what? - Sure. And I just want to back up and say, the peptide researchers that I spoke with who are here in North America suggested that there are still petri dish studies that they'd like to see done. So even more preclinical data would be helpful to better understand how this peptide is working. In terms of clinical trials, there is a phase two clinical trial that is registered right now on a government database. And that is being run out of China, looking at, I think it's BPC as a treatment for hamstring injuries. And then as part of my reporting, I spoke with a researcher at Johns Hopkins University who's currently applying for funding for a multi-center clinical trial to test BPC157 as a treatment for chronic pain. - Well, okay, we're gonna look forward to seeing what those trials show. And we're hoping that you're gonna keep us posted and up to date on everything that's happening with BPC157 Sarah. Thank you for joining the podcast. - Thank you for having me. This was great to be able to talk about it with you. - That does it for another episode of The Read Out Loud. - Thank you to Hyacinth Ambinado for producing this week's episode. - Our senior producer is Alissa Ambrose. Our executive producer is Rick Burke and our theme music is by Brian Joel. - And we'd love to hear from you. Tell us what you like about this week's episode, what you didn't like. And I don't know, what kind of peptides are you pumping into your body? You can do all that by saying it's an email at
[email protected]. - And if you like what we do, leave a review or rating on Apple podcasts or whichever platform you use to get your podcasts. - See you next week. (upbeat music)
PodcastTranscript AI