Expanding Biologics Delivery Options Via Oral Devices With Biograil's Karsten Lindhardt

Large, complex molecules present significant challenges in the formulation and absorption of biologics-based therapies administered orally. In this episode of Supplier Horizons, host Tom von Gunden talks with CEO Karsten Lindhardt of oral platform technology developer Biograil about capsule-enclosed combination devices that offer patients convenience, safety, and effectiveness while bolstering patient compliance.

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Episode Transcript

Tom von Gunden, Chief Editor, Drug Delivery Leader:

Welcome to another episode of Supplier Horizons, the series in which we talk with suppliers of products, services, and materials to the drug delivery industry about areas of the patient landscape and therapeutic needs where innovations and advancements are welcome. My name is Tom von Gunden, Chief Editor at Drug Delivery Leader and your host for the series. Today I am joined by Karsten Lindhart, CEO of biologics platform developer Biograil.

Welcome, Karsten.

Karsten Lindhardt, CEO, Biograil:

Thanks a lot, Tom, and thanks for having me to speak to this very important and interesting area.

Well, it is our pleasure to have you here. So, let's just go ahead and dive in.

As I mentioned in the intro, we're always interested here in looking out over the landscape of patient needs and potential target therapeutic areas. So, as you look out over that landscape, what do you see as some of the key patient needs and therapeutic targets that might benefit from advancements and innovations in therapies and how they're delivered?

Yes. So, definitely, we're in an area where there's a lot of activity going on. The whole biologics/peptides area is really an area of huge growth these [recent] years. We can also talk about antibodies and the whole oligonucleotides [space]. All of us, pretty much, had vaccines recently that needed to be injected. So, we are talking about a broad landscape of new drugs, new ways of [developing] drugs for patients — really redefining the way we are doing pharmaceuticals for the future. This is an area that we’re in to provide new opportunities to patients and define patients in a new way in the future, as well.

In earlier days, we talked about small molecules and everything, but now we're really trying to work with the biologics systems that we have — trying to understand the interactions of that, really allowing us to go in and interact with the physiology in an effective way, really provide a new era of active substances for patients that's really proving to be super effective.

One of the limitations of [those] types of active substances is that they're not easily absorbed. So, for almost all of these products, we are talking about a need [traditionally] for injections, either subcutaneous injections or intravenous injections. And we see a need to improve that access to patients — to get better use of these [new biopharmaceutical substances].

So, as we are broadening the scope of these different types of new pharmaceuticals, the focus on drug delivery is making [for] patients a convenient and effective way of taking these drugs, which  have several advantages. There’s the convenience part, but that's really just a part of it. And that is driving, definitely, also potentially better compliance that patients take the medications on a more consistent basis and potentially also being more effective.

So, there is a strong need to refocus our view of drug delivery. I think in the future we will see much more value in new drug delivery technologies than we have in the past, where it seems to me [that] there's been very much a drug-focused approach in this entire area. And I think we are moving into an area where drug delivery convenience and patient acceptability are becoming of crucial importance to get success [with] these new products.

Great. And, as I understand it, you are working specifically on methods for oral delivery of biologics. Tell us a little bit about how you're innovating in those areas or partnering to innovate — whatever activities are underway there to work on that challenge of oral delivery of biologics.

Yes, so we have developed an oral delivery technology, we call it BIONDD™, and it's really a capsule. And what the patients are going to experience is a capsule like any other capsule —easy to swallow. But the capsule here is special in the way that it delivers the drug. Once it is swallowed, it delivers the active substance into the stomach wall instead of what you would do with a typical tablet, where you would just release it and then it would just distribute.

The problem with these biologics, as I shared before, is that they cannot really be absorbed through by membranes and tend to be degraded in the GI tract by enzymes, by low pH in the stomach. And so, we really have what we call pure bioavailability, a pure efficiency of the drug to be absorbed in  the body.

So, thinking about those innovations that you're working on, obviously you've got an orally delivered device that you're working on. Can you tell us a little bit about the mechanism of action? What actually happens once a patient swallows this capsule? How does it deliver its treatment to that patient?

Yes. Our BIONDD™ technology is developed as an insert device fitting into a standard-sized capsule that's easy to swallow. So, when the patient swallows the capsule, it's very fast [in going] to the stomach. And because of the density of the capsule, it goes to the bottom of the stomach and basically lies on there on the floor on what we call the antrum part of the stomach, where the capsule, as any other capsule would do — it's basically a standard capsule — dissolves, and it dissolves pretty fast. When that is dissolved or weakened enough, there is a trigger mechanism, a spring-loaded trigger mechanism, that triggers an insertion element that inserts into the stomach wall. It’s made of a biosoluble material that dissolves in the tissue and then distributes the API that's embedded in the soluble insertion part.

And that means that you're really getting a very effective distribution out into the general circulation and around the typical barrier there would be for absorption of a biologic drug. So, we get a very efficient delivery of these products, and the patient is not going to experience anything because you don't feel anything [in the stomach]. The only thing patients are going to experience is swallowing a capsule. And then you're basically getting a similar efficiency out of the drug as you would from a subcutaneous injection.

In addition to the internal efforts there at Biograil, feel free to talk, if you want to, about any ways in which you, as a supplier of platforms, work with folks in the industry in partnerships and other relationships.

Yes, we have a great relationship, a good partnership, which was announced a little time ago, with Eli Lilly. We really appreciate that collaboration. We have also more recently announced a collaboration with CSL. Being able to use our technology platform to support these companies with important products on the market — that's a great part of it. So, partnership is part of our strategy, doing that if it makes strategic sense in relation to our platform build.

We are also doing internal programs. We’re also selecting active substances where we think there's a great opportunity and where we can showcase the value of the platform.

So, we have been out looking at compounds in different drug classes — antibodies, oligonucleotides, peptides, enzymes, different types of molecules — and really found what we see as the most promising of these candidates in an oral technology. And then working on that to showcase the technology, both to develop products with a potential value but also to showcase the breadth of the technology to be used with these molecular modalities.

Gotcha. And thinking about — whether it's the formulation, whether it's the alignment of the formulation or dosing with the device, whether it's the device itself and the mechanism of action — as you work to innovate and partner to innovate: What are some of the key challenges that remain to be addressed, perhaps key questions still to be answered, problems still to be solved, that are in front of you and ahead of you that you're directly focused on moving forward and advancing.

You’re starting to have some oral products on the market with enhancer type technologies, where you can get some of these biologics molecules across the board. There’s a product called Rybelsus® that Novo Nordisk has put on the market — in many ways a great technology but limited by still a very low bioavailability, still a very low efficiency of actually getting the API into the general circulation. Part of that, and part of what we have been working on, was really to make a much higher efficiency of getting the active substance into the circulation. By this type of device technology that we are developing, we have a bioavailability that's much higher than that.

Of course, because we are developing a device, it has other challenges because we are developing a combination device. It’s not just a chemical enhancement of these types of products. So, clearly there are new challenges; we need to have a dialogue with the authorities about bringing this new technology to the market and get their view and how they see that.

When you are making an insertion of a drug into the mucosa, there are certain safety concerns, obviously, that you need to address and make sure that you cover. We've already created quite a lot of data to support that this would not be an issue. But, of course, there's still a fair amount of formal things that you need to do to document that this type of technology works and [has] a general appeal in the market. Because we have to remember that there’s more of the active substance if you don't get as much in.

But first of all, [these are] very expensive drugs to produce or active substances to produce. So, there is a cost element of that. But there is also a safety element because the lower the biovailability, the less you get into the system. Often, you also have relative variation of what you are getting in from your drug delivery system. It’s becoming much larger. That could be a challenge, at least for some compounds, where you would see that the therapeutic window — that window from where you have side effects that are really not acceptable to the effect — if that is very narrow, then you cannot really just dose more and accept a higher relative variation.

So, I think from here, for the future, there is a need to find these solutions and make them effective. I'm not necessarily saying that Biograil will have the final and only solution to this. I  hope that there will be more technologies in this area because I think there's a patient need for these types of technologies.

The other thing to remember is that it's not about replacing injections entirely. That's not what we're talking about. It's really [about] giving patients a choice. In some instances, it may be better to get an injection. In other instances, it may be better to take a capsule, partly also because of stigmatization issues. A lot of people don't really like to take an injection, whereas they would be happy to take a capsule.

So,  I think there are certain times for certain types of administration forms, and it's not like replacing all [traditional forms]. It’s more [about] giving freedom to the patients to find the best solution for them in the given situation.

Great. And so, thinking about the convenience and the choice and the options for patients, as you look out over the near horizon and beyond — a last question here for you, Karsten, is really a future-pointing one:

If these advances take hold, whether they're done by Biograil and/or others, and the results are what we assume and hope that they will be, what do you envision that the lives and health of patients will actually be like once these things come to fruition?

Yes. I think we have basically just started a revolution of new drugs because the use of our biologics and our understanding of our physiology in many ways in relation to our DNA, RNA, antibodies — how they can work and interact with the body. And, for now, we have scratched the surface of knowledge, and we are really getting into better and better understanding of these things. And that opens up a chain of new, potential products in this space. But we have probably not been very good at following up [with delivery options]. We've been focused a lot on finding new targets, finding new APIs, but we have probably not been very good at really putting some resources behind finding better [delivery] solutions.

Yes, we have companies that have really been effective in that space — companies like Novo Nordisk and Eli Lilly on autoinjectors that really made that good for patients. But it has really  been directed a lot into that area, looking at various other ways of doing that [delivery] and looking at the patient population as a broad population for all types of indications and areas. I think there's a need to simply spend and focus more on solutions that go beyond that.

Well, thank you, Karsten, for the detail and the background. I appreciate your sharing your perspective with our audience. And to that audience, I want to say thank you for joining us for another episode of Supplier Horizons, and we'll see you next time.