Leveraging Nanoparticles For High Drug Load Delivery With Nanoform's Christian Jones

In this episode of Supplier Horizons, host Tom von Gunden talks with Chief Commercial Officer Christian Jones of nanoparticle technology developer Nanoform about innovation in drug and biologics delivery. The discussion covers aspects of patient centricity such as aging populations, in-home self-administration, and personalized medicine. It also focuses on the use of nanotechnology in the delivery of high concentration formulations via oral and subcutaneous routes of administration. 

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Episode Transcript

Tom von Gunden, Chief Editor, Drug Delivery Leader:

Welcome to another episode of Supplier Horizons, where we hear from representatives from supplier companies to the biopharma industry. My name is Tom von Gunden, Chief Editor at Drug Delivery Leader and your host for the series. Today I am joined by Christian Jones, who is Chief Commercial Officer at Nanoform, a medicine-enabling nanoformulation company.

Welcome, Christian.

Christian Jones, Chief Commercial Officer, Nanoform:

Thanks very much, Tom. It's a pleasure to be here and delighted to talk to you today.

Well, it's our pleasure to have you. Thanks for joining.

So, Christian, you and I, in preparation for this session today, talked about an overarching frame of patient centricity as a way to think about the work and the advances out there. And we'll specifically get into the science of high drug load formulations, which we plan to dive into.

But before we get to that, let's talk about the patient population in terms of patient centricity. We're thinking of things like convenience and adoption and compliance and, ultimately, efficacy. So, I'll just ask you to talk about what is front of mind for you and the folks at Nanoform when you look out over the patient landscape.

Yeah, sure. So, patient centricity can mean many things to different people and, ultimately, to the patient as well.

I'm minded by the aging population globally and the need for enhanced delivery for patients. The patient has got so many tablets to take, for example, particularly as they get older in the population, and polypharmacy becomes a really significant issue, as do things like dysplasia, so the difficulty in swallowing that is a known problem.

So, patients have to first remember to take their tablets or their medicines. And then, when they do take them, they have to be able to swallow them. So, innovation that can drive more patient-centric formulations, I think, is essential to support the growing population that we have and the more elderly part of that.

But, equally, also for young children that have to take medicines. And the pediatric formulations, I think, are essential. Very often we focus, as an industry, on where the majority of the market is for a certain disease. And often, particularly in oncology and areas like that, we're often thinking about older patient populations. But there are younger patient populations that also need to be served. And sometimes, they really struggle to take large tablets or many tablets.

So, making things that are easy for them to be administered. I'm reminded by a great innovation. There was somebody that invented the fentanyl lollipop for children. These kinds of innovations are making syrups and suspensions that people can swallow easily. They don't taste bitter. These are all important innovations.

But, patient convenience is one aspect, and compliance feeds into that. So, if something is easy to take, it's more likely that people will take it. If you don't have 25 or 30 tablets to take in a day — you only have 5 or 6 — you're more likely to take them. If they're easier to swallow, you're probably also more likely to take them. So, that can also have a leading effect on the efficacy and to disease progression and to treating disease in the right way.

So, I think those would be my thoughts around patient centricity on the oral formulation side.

But of course, patients don't just take oral medications. Some people have to take injections. Some people have to take respiratory medicines. And I think that, again, having easy-to-use devices, easy-to-administer formulations is essential for improved outcomes. Respiratory —COPD, and asthma — one of the more challenging treatments to overcome or to develop drugs and drug formulations for. Some fantastic devices have been developed, in the past, around treating COPD and asthma.

But at the end of the day, the patient has to learn how to use that device. Particularly, again, going back to pediatrics: they often need a spacer device to be used with their inhaler, for example. And, if they don't hold their breath for long enough, they don't get the right amount of dose delivered to the lungs. So, there's a lot of innovation going on in that space as well.

And thinking about injections, particularly with the rise of GLP-1s and the booming growth of that area. Trying to find ways to deliver injections to the body in the most pain-free way that's easy-to-use, easy-to-administer for patients. Maybe things that they could do at home rather than having to go into a clinical setting is really important.

Gotcha. Great. Great coverage in thinking about the patient population. You did mention the formulations and some of the delivery options. So, let's talk in more detail about that.

I know that, from a formulation standpoint, certainly front-of-mind for you and the folks at Nanoform is the concept of high drug load formulations. Also, given the name of the company, certainly the concept of small is important as well. And I believe, in any of this thinking, we're thinking about everything from traditional small molecule medicines to biologics and other large molecule therapies.

And so, just take that wherever you want to start and then wherever you want to go with it in terms of, why the focus on the concept of high drug load and where does the significance of small come into the picture? And then ultimately, what does that lead to when we think about the actual routes of administration and delivery forms and methods?

Sure, sure. Maybe I'll take the concept first. Small in our tagline, you see here in the logo: Small is powerful, right? So, we believe that small can actually be an ingredient in a formulation. If you have something that nobody else can make; if you have particles that are 50 nanometers, for example, and they can't be made by any other means, then you have an opportunity to introduce a novel ingredient into your formulation, albeit it's the API. Because it can have different effects, and it can lead to different types of formulation behavior.

When we first started out as a company, we were looking at improving bioavailability. That was the sole focus. If we can make particles that are smaller than 100 nanometers, we could dramatically increase the surface area and improve their solubility and help to overcome bioavailability.

And bioavailability is one of the greatest challenges for drug development today. As molecules become more complex and they go outside of the Lipinski Rule of Five, then it’s harder for them to be absorbed in the body.

So, our go-market-strategy was [to] develop the technology where we can make nanoparticles that can overcome this huge hurdle, enable more molecules to enter clinic, and increase the probability of drugs being successful in development.

We realized fairly soon that actually what we can do is similar to what amorphous solid dispersions [ASD] can do in terms of the amount of bioavailability improvement. But there's an opportunity to increase drug load. And what does that mean for the patient? Well, it means that you can have fewer tablets. You can have smaller tablets on the small molecule side.

And so that's where this idea of high drug load formulations to benefit patients has come from.

And if you think about the ways to currently develop oral medicines in the small molecule space that have to overcome the solubility challenges that are inherent across nearly 70% to 90% of all molecules that are being developed. The de facto standard now is spray drying or hot melt extrusion for creating amorphous solid dispersions.

Most of the products, I think there are about 50 products on the market at the moment in the U.S. that are made via amorphous solid dispersions. And there are hundreds, if not close to thousands, that are in development in pipelines.

The challenge, however, is these medicines — in order to overcome the bioavailability constraints —the molecule is made amorphous in a formulation step. And as a function of that, it needs to be stabilized because amorphous by its very nature is unstable. So, you have to add lots of polymer to stabilize it. And sometimes the polymer load in these formulations can be as much as 70% to 80% compared to the API that might be 20%. That leads to a very bulky formulation, which means that, if you have a dose of more than 100 mg, you are then going to have to start to think, well, I'm going to have several tablets here, or I'm going to have a very large horse pill for the patient to swallow.

What our technology seeks to do is try and create nanocrystalline particles that have the same bioavailability as an ASD but without all the need for the polymer. And so, we can make very small tablets.

Now that’s small molecules. If I [move into] large molecules, this is an area where we're using the power of small in a different way. So, large molecules are, by their very nature, water soluble. So, they normally are pretty soluble in the body. So, we're not looking to reduce particle size to increase the solubility of these drugs. Rather, the opposite. It's to have a formulation benefit.

If you look at the way that drugs are currently administered in the large molecule space. Let's take monoclonal antibodies, as an example: They're typically given via IV or via SubQ [subcutaneous] injection. With a SubQ injection, which is much more patient-centric and requires the patient to be in a hospital setting for a much shorter time or maybe even to have that administration at home or with a clinician. That could be five minutes for an administration, whereas it could be a couple of hours for an IV infusion.

So, there's a huge benefit for the patient, but also the healthcare system. And if we're looking to try and make the best medicines possible for patients, if we have an added benefit that we're also able to support the healthcare system in the costs of medicine delivery, then that's also a great thing.

So, thinking about medicines in that space: They're currently administered, as I said, by the IV infusion or SubQ administration. The concentration of the drug in a SubQ administration is typically about 100 milligrams per mil. There are one or two examples that are higher than that 150 mg per mil or maybe even 200 mg per mil. But if you have a large dose to deliver, let's say 600 mg, and it's at a 120 milligram per mil dose concentration, then that's five milliliters of injection volume that you need to deliver under the skin in a subcutaneous delivery.

The challenge there is, how do you deliver that volume under the skin? Well, you can't by standard means. So, you might need to use technologies that employ enzymes to break down the fatty tissue under the skin and create a larger injection volume. And that's what many companies are now doing.

What we're doing and what there are a few other companies doing is looking at creating high concentration suspensions that enable in a non-aqueous suspension. So, you have your monoclonal antibody that would be soluble in water, but you suspend it in a non-aqueous suspension. So, it doesn't dissolve. And by using unique technologies, you can create very high drug load suspensions of the order of 400-500 milligrams per mil. And that means that you could deliver that 600 mg dose in 1.5 milliliters.

And that means you don't need enzymes to deliver it. And it also means you don't necessarily need autoinjectors or complex devices. You can actually have simple devices.

So, that's where we're trying to use the power of small to enable the right properties of the particles so that they have low force of injection, acceptable viscosity, can be made in a sterile manner, and can basically help with ease-of-administration and patient benefit.

Excellent, excellent. Well, thanks for the coverage there of all the options and the work that's being done on the formulation side.

So, just to finish, Christian, with the way I like to end these episodes, and that is to look out over the horizon to the potential future state.

So, you can take a run at this view and any way you'd like, whether it's advances in the formulations, advances in the delivery devices, the context, and so forth. As you look out over the horizon toward a future state, what do you see out there in terms of differences in the patient experience — changes in potential benefits to the lives and health of patients, and how do we get there?

It's a great question. I think we need to embrace innovation, right? As an industry, I think we do a relatively good job, but I think we can be better. You know, one of the challenges that we face as an industry is time-to-market and trying to develop medicines as fast as possible for patient benefit. We don't always have all the time in the world to try and create best-in-class formulations. Often, if it's good enough, it gets to market, and that's what matters.

But I think being able to adopt formulation development earlier in product development is essential to create best-in-class formulations for patients that can overcome some of the challenges that patients will see going forward, can enable companies to launch with a single tablet, that could launch with a SubQ injection, that could launch with a respiratory biologic.

These are all things which are going to change the way that medicines are delivered. I think going forward into the future, hopefully, all molecules will be fully assessed for all the available technologies that are there. Rather than just saying, well, it's good enough, let's take it forward. The question every medicine developer should ask is, could it be better?

I know that time is a constant, and it's a challenge to develop things in a fast way. But I think it's the responsibility of every medicine developer to say, could my medicine be even better? And how can I benefit the patient? And by thinking like that, we're going to help ultimately create best-in-class medicines. We're going to improve patient administration. We might even have better clinical outcomes as a result of that.

And then I think the other thing that looking towards the future of medicine development, we should stop thinking about populations. We talk about patient populations. How do we treat this population? We should start to think about patients as individuals and think about, what is that individual patient need?

And I think with the growth of AI, smart devices, novel formulations — when you start to put these all together, it could be a very powerful tool to deliver best-in-class therapies for individual patients.

So, you talk about personalized medicine. This has been something that's been talked about for a long time. But I think when you start to combine all of these novel concepts, you can get something really powerful.

We think about the iPhone, right? The iPhone is really cool. It's really innovative. But the iPhone is a combination of lots of different types of innovation put together in one device. And people didn't really realize at the time that they needed it. But then, as people started to use it, they realized how reliant they were upon it and how it was a great tool.

I think, in the same way for medicine development, being able to put lots of innovation together in a smart way to get the best outcomes for patients. That's how I'd like to see the future for the pharma industry.

Excellent. Well, Christian, I want to thank you for joining me to share your perspectives with me and with our Drug Delivery Leader audience. And to that audience, I want to say, thank you for joining for another episode of Supplier Horizons. And we'll see you next time.