TL;DR

The peptide market is experiencing significant growth, driven by consumer preference for convenient oral delivery over injections. However, delivering peptides orally presents unique challenges due to their large molecular size and the body’s natural barriers. The intestinal lining, for instance, only permits molecules of a certain size to pass through, making direct absorption of many peptides difficult. Bioavailability, defined as the percentage of an administered dose reaching systemic circulation in an active and intact form, is a critical consideration. Achieving high bioavailability for oral peptides requires sophisticated delivery systems that protect the peptide from gastric acid and facilitate its passage through the gastrointestinal tract. Technologies like cyclodextrin inclusion, DEX key release agents, and sodium caprate are being developed to overcome these hurdles. While oral formats like gummies offer a pleasant sensory experience, engineering them to deliver peptides effectively and with comparable efficacy to injections is a complex scientific endeavor. The growing market investment in peptide research and development is now accelerating solutions to these long-standing bioavailability challenges, aiming to make oral peptides a more viable and effective option for consumers.

The Growing Demand for Oral Peptide Delivery

Will: And I’m Will West, the co-founder and CEO of the Tesseract life sciences family of companies. All right. We’ve got some great perspectives here today. Let’s get into some of these questions that I think are going to be really interesting. Today we’re going to be talking specifically about oral peptides, peptides, gummies, and the bioavailability problem surrounding these. Our main focuses again are going to be on again, peptide gummies, oral peptides. Bioavailability, absorption, delivery systems, sodium cap rate, liposoma, and cyclic dextrin inclusions. We’ll obviously get into a lot of other topics, but those are going to be some of the big things that I think will interject into a lot of the different questions. The first question that I have today is: why are oral peptides and peptide gummies becoming such a high-interest topic in the peptide market?

Will: Well, I I think there’s there’s a couple of reasons. The first one is people don’t like to take shots or give themselves shots. And that’s that’s where the market is. That’s that’s where it’s been, that’s what has been available. And the market has and has continued to explode, even though that’s the only thing that’s been available. Which just shows you how massive the interest in peptides has been, and how much growth that it’s already exhibiting and how much growth potential is out there, despite the fact that people have to do that when they don’t really enjoy it or don’t want to in most cases.

But the broader markets, the markets for supplements, for instance, have already shown us what the trajectory looks like.

Will: People prefer oral products, they certainly prefer gummies. Chewables, things that have a flavor, a flavor system, a sweetness, a taste profile that reminds them of something favorable. If a market can make a transition from something that people really do not like, such as an injection, to something that they absolutely prefer, and in many cases they compare to a candy, then that’s a natural and desirable transition. And people are not only willing to pay a lot for the peptide they’re willing to pay for a desirable experience on top of it.

Ulli: Yeah, I think there’s really nothing to add to that. The the idea of injection is very objectionable to most consumers, especially if they have to do it themselves. If they don’t want to do it themselves, it adds an additional complication of having to go to The doctor, having them recommend the peptide, having to make an appointment, going there, getting the injection. Most people don’t have time for that stuff. And so if you are in any way, shape, or form, you have trepidations about injecting yourself or getting injected and the complications related to that, then of course you would be super interested in buying an oral peptide.

Will: Yeah, and trepidation is a great thought here.

Half the time we end up laughing behind the scenes when we talk about some of these things, but people worry are they going to do an injection wrong? Is there a right place to do it? Is there a wrong place to do it?, should they be doing it, just under the skin? Does it have to go in the muscle? What if they mess it up? And a lot of people, if they want a peptide, they’d probably be injecting themselves for the first time. They’re they’re particularly concerned about it. I’ve never once had a person ask me, what if I chew the gummy the wrong way?, it’s not the thing that they’re worried about messing up.

Understanding Peptide Bioavailability Challenges

Will: And so it takes all the fear factor out of it, it takes all the guesswork out of it. People know how to eat a piece of candy or chew a gummy. It’s it’s just a very sensible solution for them. It’s ease of use., yeah, it makes total sense. Every single industry that we’ve seen any massive interest even when there’s a strong barrier to entry, when you take away that barrier, the floodgates open. That makes total sense. Next question being so what’s the basic bioavailability problem that makes oral peptide delivery more difficult than standard supplement delivery?

Ulli: I do think that the overall you call it the bioavailability problem. That applies to most peptides, not even just the oral peptides. It’s it’s much more pronounced in oral peptides than it is for injectables. There’s really two big factors that I am, always trying to look out for. Number one is so peptides are designed, right? There are a lot of peptides in the body already, but usually the peptides that are available in the market through a compounding pharmacy or a doctor or Prescription, they are designed, so they’re biologics, and they’re usually very large.

They’re very large molecules, and there is a permeability problem when you take those orally because your gut wall, your intestinal lining, only allows molecules of a certain size or smaller to easily pass through the gateways in that in that intestinal lining in the gut wall.

Ulli: Enter your system. The other one, which is also quite important, is that most peptides hate water. And so they do not want to disperse and dissolve in water easily, which that makes it even worse because, as we all know, the majority of our body composition is water. Therefore, if something is hydrophobic, it hates And that’s why in general, in general, I would say the natural unenhanced bioavailability of a peptide is in the single digits. When you look at the research, obviously there are hundreds of peptides, some are more absorbable, some are more bioavailability maybe into 40 or 50 percent. But the lion’s share of the sheer number of them has very poor bioavailability.

Innovating Delivery Systems for Oral Peptides

Will: Yeah, there’s another lens as well that you can use to think about this, which is when it comes to the oral delivery of a peptide, you have to get it past the stomach. And then you have to get it into the system. And neither of those things are easy. First, getting it past the stomach acid is difficult because the peptides are fragile, and so you need a reliable system to do that. And then when it comes to getting it into the system, as Zuli points out, and so in order to get it into food, you need a way to facilitate the body’s absorption of the peptide in the gastrointestinal tract., fortunately, this is what Tesseract excels at. We’ve done that for years in the supplement, the nutraceutical, the medical food world, to some extent, our IP or patents of work extends into the pharma world, which is what is getting us into the peptide space.

Will: But those challenges persist quite dramatically with peptides. One of the things that you mentioned early on of or cyclodextrins, to use that as an example, there are there are systematic approaches to use cyclodextrin delivery to get things past the stomach and into the gastrointestinal tract, which is the first challenge. You definitely need a way, there are other ways to get it past that stomach acid, otherwise the peptides are going to. Be destroyed. Anything you take orally is has that challenge. But once you get it past the stomach, then you have realistically an even bigger challenge of getting it into the system because the body can’t do anything with it just because you get it past the stomach. And so our patents in that area, facilitate the opening of the tight junctions in the in the gut wall to facilitate that absorption because peptides.

Will: For the most part, they’re going to be too large to easily pass through those tight junctions in the gut wall. And if they don’t get through there and into the body, they’re not doing the consumer or the patient any good. And every company that’s a brand entering the peptide space has to confront that challenge and is going to need a solution to those two problems. Every patient or consumer who’s thinking about Peptides is going to have to ask the question whether or not the peptides they’re sourcing have solved that problem. Otherwise, they’re they’re totally wasting their money. That’s a really interesting point. And I think that both of you guys brought up is on Uli’s side, I think just even the misnomer of the question in and of itself to start, of it’s not just a question of the gummies via bill.

Will: Bioavailability, but overall bioavailability of peptides. But then yeah, the the idea, I think not many people when they’re thinking about the end result, are thinking about the whole process. But I think it’s important to tie those two when you’re really when you’re looking at it as a consumer.

Ulli: I wanna I wanna just mention this. I know that the term bioavailability is all over the place. And So one of the things that’s important to keep in mind is that bioavail bioavailability is the percentage of an administered dose that reaches the systemic or bodily circulation in an active and intact form.

That’s important because that’s different from absorption. Bioavailability means that if you let’s say You administer a hundred percent of peptides. And this peptide is a peptide that has a 1% bioavailability. That means that at some point, maybe an hour, two hours later, you will only be able to measure 1% of that peptide in the body. That means that you lose 99% because of. What Will was talking about, passing through the esophagus, passing through the stomach and gastric acid, in the ability for that peptide molecule to cross through your intestinal lining into the system, because usually that bioavailability is measured in the bloodstream.

Ulli: And so it has to go from your gut through the intestinal lining into your body’s circulatory system, which obviously has a lot of different channels, but one of them is. Bloodstream. And so when we talk about bioavailability, that’s what we’re talking about. When we’re talking about absorption, we are talking about the ease with which a molecule can pass through bodily barriers. They’re related, but they’re not the same. That is a real I’m glad that you brought that up. Those are really useful again as a consumer on the side of these things, you don’t ever think to even ask those questions, which I think is so helpful.

Ulli: Yeah, and everybody talks about it, everybody knows somewhere that bioavailability and high absorption, high bioavailability and high absorption are both very good. Yeah. That’s great. But as an educated consumer, you want to make sure you understand what that means and what those two Characteristics tell you about the efficacy and quality. If you buy a vial of peptides and it’s $499 and the bioavailability is 1%, we can all do the math how much money you paid for nothing. Right? Yeah. That’s how it works, right? Nobody would buy a car if you can only drive one percent of the car after you spent, forty or fifty thousand dollars. This is something. Important to keep in mind.

Will: That’s a that’s a fantastic way of putting it. You’re so right. It with almost any other product we think about it that way. But somehow with this being such a yeah with this being such a high price or high cost, really dense product, obviously that’s where things come into play. We I think we’ve we’ve answered this question because you guys have been so thorough in the last question. But if you maybe even want to take it in a different direction, I’ll just I’ll I’ll still go for it. But why are consumers attracted to gummies, capsules, and other formats even when injectable peptides dominate much of the current discussion? And I almost wanna point towards is it is it d what we just talked about? Is it the bioavailability? Is it the what part of that do you think comes into play?

Hendrik: I I think it’s an important topic. The question itself is exactly backwards. The question is, why do the injectables dominate? And the answer is because it’s it’s so hard to get to an oral form of peptides that are so highly available, bioavailable, and absorbable, that they can compete in the market. And Now that the market has grown and it’s clear that there’s an investment case for brands and manufacturers, they’re applying a lot of time and energy and financial and human resources to these problems because they know there’s going to be a massive financial return when they do.

But it’s it’s a challenging set of questions to tackle.

Hendrik: And so we know the market. It’s there, we know the demand is there, supply has to catch up. But historically, the market and the conversation has been dominated by injectables because it was what we had, it was easier. The business case was there, the technology was there, and it simply wasn’t there technologically on the oral side., fortunately, there are already answers. To the oral equation. And we know that, from the Tesseract point of view, we’ve already helped a number of clients with them. There are others that are making strides in those areas, but the market is nascent just because it’s it’s a newer part of the equation.

Ulli: Yeah. And, in terms of delivery, it’s interesting because. An injection is in for a human body is the most direct application of any ingredient into the system, right? Because you bypass everything, you bypass swallowing or chewing or swallowing and digesting and stomach and intestinal walls. Going directly into either the muscle or the bloodstream, obviously, you have many less. Barriers, this peptide solution has to overcome. But again, it’s related to injection, it’s related to a needle, it’s related to, are you comfortable doing it yourself? Do you need someone else to do it? When you think about oral, then you add a curve. You add this idea that it has to survive the somic acid, it has to find a way to get. Through the barriers and the lipid layers in the intestinal tract.

Ulli: And then the size of the molecule becomes even more important, right? Because the cells in your intestinal lining, they have a particular size opening. If you have a two-free two-foot-wide door and you bring in a six-foot-wide piano, it is not going to work. And this, but this is, I know this is a very hokey example. But this is truly what this often looks like. And so there is an incredible desire for oral administration. It’s a pleasant experience because it’s sensorial, you have a taste, you have a texture, but it is so much more difficult and so much more challenging to deliver the peptide, even a fraction with a fraction of the efficacy that you get from an injection. And obviously, one of the Reasons we’re here is because we have technologies that solve for that challenge.

Ulli: We have technologies with cyclodextrin inclusion, with the DEX key release agent, with our sodium cap rate that address all these issues, be it protecting the peptide from gastrointestinal from gastric acid, protecting it on its way to the intestinal layer, making sure it opens up in the intestinal. In the intestinal tract, and then helping the cell walls off the intestinal tract to open wide enough to welcome. I go back to my Holy experience, the six foot piano into the living room, and then without any long term or even short term effects, close back up and the piano is safely inside and can do its job.

Comparison at a glance