Leveraging Janus Base Nanoparticles For Precision Therapeutic Delivery With Eascra's Mari Anne Snow

A major challenge in delivering biologics-based therapies is penetrating cells for precision delivery to therapeutic targets. In this episode of Supplier Horizons, host Tom von Gunden and CEO Mari Anne Snow from platform technology developer Eascra Biotech discuss the use of Janus base nanoparticles to effectively and safely encapsulate therapeutic payloads, including CGTs and other large molecule biologics. The conversation also turns to the benefits of particle production conducted in space. 

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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 the series. Today I am joined by Mari Anne Snow, who is cofounder and CEO at Eascra Biotech, a platform technology development company. We'll be talking about the approach of using Janus base nanoparticles in the delivery system. Before we get to that, I just want to welcome you, Mari Anne. Thanks for joining,

Mari Anne Snow, Cofounder and CEO, Eascra Biotech:

Tom, it's my pleasure. Thanks so much for having me.

Well, it's my pleasure to have you here. So, let's start by talking about what you see and the folks there see as you look out over the landscape of patient needs and therapeutic targets. What are you focusing on? What do you see where you believe that the work being done at Eascra Biotech can help?

Eascra Biotech is a nanomedicine company that supplies therapeutic delivery solutions. And we think that this is a critical element when you're talking about drug discovery today. Because one of the things  we absolutely know is that the lack of capabilities to be able to target specific cells or tissues for delivery is a big bottleneck when you're talking about drug development, particularly for genetic medicine or some of the emerging types of treatments that are coming online today. We know that candidates are being discarded at the cost of millions of dollars because of either toxicity or inability to be able to actually penetrate their targets and deliver a therapeutic agent to their targets. And we know that this is going to continue to be an issue until we start introducing new types of delivery technologies that can overcome some of the functional limitations. And that's really where we see ourselves providing a next-gen solution for targeted drug delivery.

Gotcha. So, before we get into the specifics of the science and technology that you're working on there, what have been the historical or current approaches to some of the therapeutic targets that you're planning to address? What has been available to patients, with what effect, and with what limitations or constraints?

So, if we’re talking about drug delivery in general, obviously, lipid nanoparticles really rule the day; they own about 80% of the drug delivery market at this point. Plus, there's been a history of AAV delivery, peptides, polymers, gold nanoparticles — a variety of particles that are in the market and have been used for some indications.

Now, part of the challenge has been really focused on, first of all, all of these — the majority of these—  mechanisms are spherical in shape, right? They're a little sack. And that little sack has size constraints that have really had a big impact on capacity — the delivery technology’s capacity to penetrate a cell and tissue, and then also maintaining cargo bioactivity for extended periods of time, not triggering the immune system. These are still functional problems that have to be overcome.

Gotcha. Well, I think it's time now to talk about the work that you're doing there. So, as I understand it, the platform is essentially based on a concept called Janus base nanoparticles. So, tell us a little bit about what that is and then also weave that into the routes of administration through which those can be delivered, the kinds of therapeutic payloads that can be encapsulated or contained within it. And then anything you want to say about mechanism of action once a patient actually receives something delivered in this manner.

Sure. So, Janus base nanomaterials are a technology that was developed by my business partner and cofounder of Eascra Biotech, Dr. Yupeng Chen. He's a biomedical engineer and associate professor of biomedical engineering at the University of Connecticut. So Eascra is a UConn spin-out, an academic spin-out. The technology has been developed over about 20 years, so it's something that has been refined in the lab. And for the last four years, we have been working to transition it to the commercial market because of the need.

Janus base nanoparticles are unique in the sense that it's a synthetic biology. It's a synthetic molecule that was inspired by DNA. It's a base molecule that has two DNA base pairs with a customizable side chain that we can modify at the beginning of the production process for a specific cell or tissue type. And at Eascra, we've been working very hard to build a library of base molecules that can target a specific therapeutic area depending on the objective of the therapy that's getting developed.

Janus base nanoparticles, we call them JBNps, actually are a completely new construct in the sense that, rather than a spherical shape, they self-assemble into a tubular structure. They're long, slender tubes that bundle around a cargo and encapsulate that cargo so it actually renders it room temperature stable.

So, we can take a very fragile cargo like an mRNA or other types of cargo, which traditionally have to be maintained at very low temperatures, and keep it stable and bioactive for months at a time. And we can also, because of the tubular structure — that long slender tube — we can accommodate a wide variety of payloads. So, we can not only encapsulate a small molecule, an siRNA, an mRNA, proteins, peptides, we've also actually encapsulated Cas9. And so, the reason that we have that capability is because the tubular structure allows us to be able to accommodate both a small size and a large size.

And then the advantage that the structure has because of its long, slender shape: it's only 10 to 20 nanometers in diameter. So, at its base — think of it as almost like a little heat-seeking missile — it's more of a spear structure. And that means that we can penetrate hard-to-penetrate tissues, which traditionally have been quite difficult, like cartilage, like kidneys, like ECM [extracellular matrix]-rich, solid tumors. And we can actually penetrate those cells through endocytosis. And then once inside the cell, because we have a non-covalent bond structure, the pH change inside the cell is actually allowing for release.

And you were talking about how is this administered? We've actually done this not only through direct injection for joint treatments, but also through IV drip.

Gotcha, gotcha. So, tell us a little bit about where you see the company, the organization, and the science and technology that you're providing fitting into the larger ecosystem of how therapies get delivered to patients. Tell us maybe about the founding and where you see yourself in terms of partnerships and licensing, whatever model would be the commercial version.

Sure. Eascra has a very unique history in the sense that, first of all, we launched at the beginning of a very down time in the biotech life science market. We actually launched at the very end of 2021. So, any type of funding for biotech startups at that particular point in time, particularly if you had a preclinical product, was pretty tough. And so, one of the unique aspects of startups that have managed to sustain themselves is being creative, innovative, a little scrappy.

And so, we took a little bit of a non-traditional route to start, which is we were able to capitalize on some existing relationships that we had with NASA. And NASA evaluated our technology and identified it as a candidate that was very well suited for being produced in space on the International Space Station. So, our first funding actually came from NASA. And Eascra — four years into our history because we'll be celebrating our fourth year anniversary this November [2025] — four years into our history, we have not only been able to travel to space with the product five times, produce it in space, [but] we're the first company to ever produce nanoparticles in space for commercial use on earth.

And if you take stuff to space, you also have to test it on the ground. So, even though we weren't planning on being a space company, we discovered as a startup that we could generate a huge amount of validating market data because anything that we did in orbit, we also had to conduct on the ground. So, four years in, we have not only completed five missions, we have extended our grants, and we'll continue to do space work as we are also continuing to do our ground work. And as a result, we actually have an ongoing sponsored research partnership with a top 10 pharma company that we've been working on now for the past eight months.

Gotcha. For those in our audience who may not be familiar with the advantages or the promise of production in space, tell us a little bit about the concept there. Why space?

So, one of the things that we've learned in the process and over the time period that we have been working with the space community is that space science and life science have had a long, long history that most people are probably not familiar with. And we're not just talking about one-off experiments. Companies like Merck, companies like Bristol Myers Squibb, large pharma, notable pharma, have actually been utilizing low earth orbit for things related to protein crystals. Because if you actually take protein crystals to space and you form them in space, not only are they more uniform, more homogeneous, but they're very structurally stable. And protein crystals start as particles in water or particles in liquid. And while we're not a protein crystal-based structure, we are synthetic molecule, we start as particles in liquid. And so, our assembly process actually benefits from the lack of sedimentation, friction, convection, and the resulting structures are about 40% more effective. We're already effective on earth; we're already getting good results. We already have functional capabilities that exceed the current delivery mechanisms. But turns out when we take them to space, when we build them in space, they're 40% better.

Interesting. So as the work advances, are there additional problems to be solved or challenges to overcome? What's next up to address and move forward in terms of continuing to advance the approach?

So, Eascra is actually committed to parallel pathways. And part of that is because, how many times do you get to be a pioneer innovator, and be a pioneer innovator where first mover advantage means that, as these ecosystems advance — and they're advancing very rapidly right now, by the way — then that means that the people who have a presence, who have an ecosystem, who have relationships and also the expertise are going to have a big advantage as these ecosystems start to formalize, as supply chains are really, fully realized, and as regulatory pathways are finalized. These are all things that are in process.

But all of that takes time. So, as a life science company, we are aggressively looking at ways to advance the technology here on earth in a more traditional pathway. So, we are continuing to aggressively build validation data. We are establishing proof-of-concept to our capabilities to be able to be good collaboration partners to pharma companies, gene-editing companies, and biotech companies that need delivery solutions. So, we can contribute to their therapeutics and do that in a way so that we can validate the technology. We can start to develop our own products in house. And we can really contribute to overcoming some of the major challenges in the industry today related to drug delivery, targeted, particularly targeted, specific drug delivery.

Gotcha, gotcha. Well, Mari Anne, I like to end these episodes where we started, and that is by looking out over the patient landscape. So, we started by looking at that historically and currently. I'm going to invite you to look out with me further out on some horizon, whether that's near or far. And as the work advances and lives up to the promises that we anticipate, what do you imagine the life and health of patients might be like should some of these advances land in that landscape?

Some of the really exciting things that get us out of bed every day, particularly because, like most people today, our personal lives have been touched by folks who have had debilitating diseases like osteoarthritis or have been really impacted by cancer. And if we can help to produce therapeutics that can not only have a positive impact on tumor reduction, but in the process could provide systemic protection so side effects are lessened. Because right at this point in time, we know that traditional oncology treatments are always kind of a balance between how do we kill the cancer without killing the patient? So, if we can reduce systemic side effects while we're also having a positive impact on tumor reduction, that would be, it would be so wonderful and so amazing.

And then chronic diseases like osteoarthritis, they're impacting one in four humans. It is a debilitating disease. It costs people a lot of money. It's one of the leading causes of disability in this country. And if we can offer an actual therapy that can interrupt infection, retain cartilage, reduce disability, but also reduce pain for people, that would be fabulous.

Yeah. Well, I appreciate the passion and the commitment that I can hear coming through as you describe those things. Mari Anne, I want to thank you for joining me to share your insights with our 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.