Enabling Oral Delivery Of Biologics With Vivtex's Thomas von Erlach

The rapidly expanding demand for biologics-based treatments for chronic, metabolic diseases has spurred a desire for oral administration. Videocast host Tom von Gunden talks with CEO Thomas von Erlach from delivery platform developer Vivtex about using high-throughput screening, advanced computational tools, and formulation technologies to drive higher absorption and bioavailability of peptides and other macromolecules delivered via gastrointestinal routes.

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Episode Transcript

Tom von Gunden, Chief Editor, Drug Delivery Leader:

Welcome to another episode of Supplier Horizons. My name is Tom von Gunden, Chief Editor at Drug Delivery Leader and your host for today's conversation. Today, I'm joined by Co-Founder and CEO Thomas von Erlach from Vivtex, an oral platform delivery developer.

Welcome, Thomas.

Thomas von Erlach, CEO and Co-Founder, Vivtex:

Thank you, Tom. Glad to be here.

Yes, well, it's my pleasure to have you here. So, we'll hear more about the oral delivery platform approaches that you and the folks are working on there at Vivtex. But before we get into the science and technology, let's talk about what you and the folks there are looking at when you look out over the patient landscape.

What are some of the current indications, current patient populations, traditional approaches and experiences that you believe that the work that you're doing there may help to improve and advance?

Great question. So, what we do is, we focus on trying to overcome the oral delivery challenge for compounds that really suffer from insufficient oral exposure. So, that really means that without any help or technology, those compounds would be limited to needle administration. The compounds that are in this class, typically, are in the macromolecule category.

A prominent example would be peptide therapeutics. A big issue that we currently face with peptide therapeutics is that, for the most part, they’re really still limited to needle administration. And what we see right now versus, let's say, the last few decades: peptides therapeutics have really become more and more popular thanks to the innovation that has happened in this field.

So, really, the ability to create extremely potent therapeutics and therapeutics that can hit targets that traditionally only monoclonal antibodies were able to hit. This has really been driving a wave of peptide therapeutics that would really be able to treat a broad range of indications and patient groups.

When I look at the current landscape, I would say being able to deliver those macromolecules is more important than ever, because right now we really see a bit of a shift in those peptide therapeutics becoming more and more prominent, the different indications, and having the promise to potentially add or even substitute existing monoclonal antibody therapies out there.

So, when we think about the indications, I think you could say any patient would really prefer to take their medicine via the oral route instead of an injection. But there are certainly indications in patient populations out there that, you could say, would benefit the most.

And, when we look at that, we would certainly say that if you are having to take your medicine on a chronic basis, potentially even daily injections, then that is a really big impact on the quality of life. And any substitute, alternative of that medicine will really have a big impact in the patients' lives and also the adherence of the patients to that medicine.

So, being able to focus on indications where we see chronic dosing and frequent dosing is very high on the list. Right now, the metabolic disease space is certainly a good example to point to. So, diabetes, obesity, these type of indications, obviously, do have chronic dosing. They also do have a very large number of patients that we can reach, so that's typically another motivation to really invest in an oral technology or substitute the fact that you do have a lot of patients that you could serve with that.

So, besides the actual metabolic disease space, I would certainly also say that the autoimmune disease space is very high on the list as well because of, again, large population and chronic dosing.

Great. Well, thank you for providing a survey of what's out there that you're focusing on. So, now let's move into the science and technology that you're working on there. As I understand it, the origins of Vivtex are at MIT and work that you were doing there in association with Dr. Robert Langer and the folks there.

So, tell us about how it got started and then the carried forward into Vivtex, and what you're actually working on, developing and providing. What's in that platform, and how should we envision what it can do and what it might do?

Sure, yes, happy to. So, my background is in tissue engineering. That's what I focused my PhD on. And then  joined Robert Langer's lab at MIT as a postdoc a number of years ago. During my time there, I also met Giovanni Traverso, a very talented MIT faculty member and also GI doctor.

And the three of us, with Bob obviously having a big, historical focus on drug delivery, including oral, really thought about what would be a very impactful approach that would add an improvement to the existing field and technological capabilities out there to deliver drugs orally.

When we looked at this, we really felt, what we have with the GI tract is an extremely fascinating,  complex organ on a tissue level. So, we have not just an extremely complex tissue layer that changes as a function of the GI segment, but we also have a mucus layer sitting on top. And that is a very interesting structure we have that evolved over many, many years of evolution to essentially enable us to absorb certain chemicals that the body needs, certain nutrients, but avoid harmful chemicals to reach systemic exposure.

So, it's an extremely sophisticated and complex barrier function that we have in our gut. And we felt that if we really want to make sure that we can trick those barriers in absorbing a drug that would otherwise not be absorbed, we need to be able to capture the entire complexity we have in the GI tract. And use that to systematically evaluate different ways how we can conduct these screening experiments, if you will.

What we've done is found a way for how we can take the GI tract, the entire GI tract, out of animals or also humans and maintain the viability of that GI tract for an extended period of time. And then we combined this with a screening assay that we created that essentially enables us to use the actual GI tract for fully automated, high-throughput screening experiments.

And that enables us to conduct a wide range of testing to evaluate what drug delivery approach we could use to overcome the GI barriers versus what otherwise would have needed to be limited to in vivo testing, which obviously takes a lot longer and the actual number of samples that can be tested is not nearly as much. So, as a whole, that's really the technology we focused on building and using.

So, initially, over a number of years at MIT, and then in 2018, we started Vivtex — me, Giovanni Traverso, and Robert Langer — the three of us co-founded the company. And then, over a number of years now, we have further built the capability of the technology. A big focus has really been on adding computational tools as well, so we're not just able to use the experimental high-throughput screening capability, but also new, cutting-edge computational tools.

A big motivation for that has been to be able to make sure that whatever we see in a well plate, in a screening assay, is ultimately going to be possible to be translated into a solid dosage formulation that basically ticks off all the boxes required to be clinically and commercially viable. So, you're really trying to build the platform towards the ability to get to that point in the most efficient and fastest period of time.

And that took us a number of years to establish and, now, since about two years, I would say, we've been able to at least meet that milestone of being able to put forward our first generation of drug products, and we have a number of those in preclinical development. And the lead candidate is

currently in Phase 1.

So that's where we are currently as a company.

Gotcha. And as you continue to work, to move the advances forward, are there any particular challenges to overcome or problems to solve or questions to answer that you and the team there are heavily focused on?

So, despite us having been able to get to a point where we feel like we have created new products that are able to be moved forward, which obviously is very exciting for us, there's still a lot of room for improvement in what we can do collectively. I think the room for improvement is to our ability to further increase and push the boundaries in terms of oral exposure.

So, right now, we think some of our current capabilities would say that perhaps we are comfortably able to be in the high single digits, maybe low double digits. That’s in terms of absolute oral bioavailability. But I think with more work by us, or maybe others, this could be further increased.

And I think that would be a really big improvement to the field when it comes to cost of goods of the actual therapeutic. The ability to reduce the amount of dose needed would obviously be a huge improvement. And in many cases, we see that it's still very hard to deliver certain therapeutics orally.

So, I think we really are still, I would say, in a phase right now where we are seeing some successes; we are seeing some oral peptide products coming out. Novo Nordisk has been, obviously, pioneering this with oral sema[glutide], with Rybelsus and Wegovy coming out.

Some of the existing efforts, including by Vivtex, give hope that we can look forward to a next generation of oral products that are going to be even better. I would like to think that there might even be a third phase that we could work towards, too, that would even further push the boundaries on the oral exposure.

But also, something that we are currently working on — and I would see big potential in the future — is not just worrying about the actual oral exposure, but also about how we actually take these oral medicines, meaning the actual dosage restrictions that a patient has. So, just because it's a tablet doesn't mean it's equal when we look at the different oral drug products. Some you can take with food; some you really have to take on an empty stomach and wait until you can drink and eat.

Unfortunately, right now, with peptide therapeutics, with technologies out there that enable them to be orally bioavailable, we really are in this latter category. We are having to worry about being able to perhaps reduce the time it takes until a patient can take food or drink. Potentially in the future, it would be possible that the drug could be taken even with food, but that is something that we don't see right now as a possibility, but perhaps in the future.

But as a whole, I think we can safely say that the ability to make it easier for the patient to take the medicine is still a big area of improvement that we focus on. I think others, too.

Good. Well, you are already starting to point toward the future with talking about next generation and so forth.

So, I like to end these discussions with looking out over the horizon, whether that's near or far, however far you believe that the future state can arrive. As you do, whether it's in the receiving of a therapy experience for patients, or whether it's in the bioavailability that you mentioned or the efficacy or the treatment or cure or management of chronic diseases: If these advances that you're working on take hold, what do you imagine might be different in any of those areas for patients and their experience and their conditions?

I would love to see that, for pretty much any medicine, any indication out there, ultimately we are able to put forward an oral drug that people can take. Now, perhaps even at the far distant future, maybe one would look back and really wonder why people had to take their drugs as injectables on a regular basis.

I think we'll always have needle administration, but perhaps in the future, more as a singular medical intervention as opposed to a way of living for some patients that have to take this every day for the rest of their lives. So, that would be my dream, and I think something that ultimately would really have a big impact for many, many people out there.

I always remember the saying that drugs do not work if people don't take them, which sounds very simple. But I think it reminds us that, when we look at patient adherence, there are statistics out there that suggest that about 50% of the patients do not take the medicine the way they should. And that, in itself, obviously has a huge impact on the treatment outcome.

So, I think having an ability to make it the easiest way possible for patients to take the medicine. And obviously taking it through the mouth is a very natural thing for us. That’s where we are typically taking food, and it seems something that will probably be the least invasive in terms of our normal life. So, if we can enable that for pretty much any new medicine that comes out there, I think that would be fantastic.

One aspect that is really justifying us to continue pushing on the delivery field is, we are not having less new drugs come out that are either in need of technology like ours or would otherwise need to be administered via needle injection. So, we still have a lot of drugs. And if you look at the new generation of drugs coming out there, a lot of them are really limited by the issue of having insufficient oral exposure. So, I think we really have to try to tackle this.

A key aspect we have to worry about is that, when we're trying to tackle drugs, it's very hard to know which drug really is amenable to oral delivery versus which one isn't. So, one thing that we also see as perhaps a glimpse into the future is that, instead of trying to reduce the development timeline and the R&D spend, one could really imagine a future where we are already in a discovery stage, are able to select which of the candidates might be more amenable for oral administration versus others.

If we can incorporate that in the efforts that we do, I think we can really look forward to a future where ultimately most of the patient indications that we are trying to serve out there would be able to have an oral option.

Got it. Well, listen, I really appreciate hearing about the thinking and the work that's going into it around things like patient convenience and adherence. And also, obviously, therapy bioavailability and efficacy. And perhaps even the expansion of therapies and drugs that can be delivered orally.

So, Thomas, I want to thank you for joining me for this edition of Supplier Horizons and sharing the work that's being done there by you and others at Vivtex. And to our audience for Supplier Horizons, I want to thank you for joining again, and we'll see you next time.