Protecting And Sustaining Biologics Via Microencapsulated Delivery With Likarda's Stella Vnook

A common challenge in administering cell therapies and other biologics-based treatments is sustaining delivery and bioavailability while protecting against degradation and off-target toxicities. In this episode of Supplier Horizons, host Tom von Gunden discusses with CEO Stella Vnook from platform technology developer Likarda methods for deploying hydrogel microencapsulation to safely route cells, proteins, and other biologic agents to therapeutic targets. These include long-acting formulations in oncology, immunology, and other chronic or rare diseases. 

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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 Dr. Stella Vnook, who is CEO at Likdarda, a company working on platforms to deliver cell and other biologics-based therapies, focusing on encapsulation as the primary mode of the platform, and we'll hear about that.

So, welcome, Dr. Vnook.

Dr. Stella Vnook, CEO, Likarda:

Thank you so much, Tom. It's really a pleasure to be here.

Well, it's my pleasure to have you here. So, let's just go ahead and dive in. So, Stella, why don't we start by looking out over the patient landscape and the therapeutic targets out there, and tell us a little bit about what you and the folks at Likarda see out there that has you thinking about the kinds of platform delivery technologies to address what's out there. What therapeutic targets, what kinds of patient needs, are most ripe for the technology and the science that you're working on there?

It's a great question. So, Likarda actually started out focusing on diabetes and then progressed into osteoarthritis. The initial focus in diabetes was primarily to solve the issue of, how do we deliver islet cells? Because the failure rate was pretty high.

Then after Likarda had bravely encapsulated islet cells, they progressed into targeting encapsulation of liver cells. So, that opened the path to oncology and other autoimmune disorders: osteoarthritis, rare diseases. So, all the demands to have a more controlled, sustained delivery.

So, in my experience, I've been doing this for 25 years, primarily launching therapeutics, realizing that drug delivery is often a hidden bottleneck, allowing us not to realize the full promise of the advanced therapies. So, in any modality or any therapeutic where you think maybe you want to deliver something more in a sustained delivery fashion — maybe it's a fragile therapeutic like cells, or maybe you want to reduce number of injections because it's a huge burden for the patient. That's really how I think about where we would fit in.

Gotcha. And before we get into the specifics of the science and technology there — how the platform is designed and what it does — what would be on the market already or what methods would have been already tried? Or what is currently used to deliver the therapies in the ways that you are working on a different kind of approach to do so? What's available now?

Well, most therapies right now are delivered systemically. So, we're talking about IV infusions or quite frequent injections. [There have been] products that have implantable pumps. [All of] which is interesting from the industry perspective because this has led to a paradox where we have engineered miraculous therapies, but the way we deliver them can undermine the efficacy or drive up the costs, or even worse, limit patient access.

So, when we're delivering the therapies the way that I just described, drugs often get diluted, degraded, or cleared quickly. So, some of the limitations that we currently see are high dosing, which leads to off-target toxicity. Obviously, there's cold chain logistics implications because most therapies have to be delivered on liquid nitrogen, something that we avoid with our technology, and they're costly, right? They're difficult to scale. So, this is why these therapies — even though they're very transformative, in theory — in practice, they remain expensive and fragile with limited access.

Gotcha. So obviously, you are working on technologies and a platform that will get around some of those constraints, if not all of them. So, tell us about that. How is the platform designed? What does it do and how does it work? How is it designed to work more effectively than what you just described?

So, to take a broader perspective, we are a true microencapsulation, right? So, we target to deliver these therapies through either SubQ [subcutaneous] or localized implantation, right? This delivery really is a promise to enable more therapies to patients in a scalable manner.

So, our Core Shell Spherification [CSS] technology, I think of it as a next generation encapsulation platform for biologics, proteins, or for live cells. So, how does it work? So, it's a core shell. That's what it is. We create tiny hydrogel spheres, anywhere from 200 microns to 1,000 microns. An average therapy is about 400 microns that protect biologics and cells and allow for very controlled release directly delivered to where it matters — for example, a solid tumor. That becomes really important when we are talking about providing a long-acting, sustained release version of the product.

So, instead of frequent injections or infusions, for that matter, we can deliver a steady, controlled dose over weeks, months. That improves not only efficacy, but reduces the highs and lows of the bioavailability curves and dramatically lightens the patient burdens.

So, it depends on what kind of therapy we're talking about because, for biologics and proteins, it's really all about sustained release because we want to improve adherence. For cell therapies like CAR Ts and Ks [K-CAR Ts]. It's really important to consider that, when we encapsulate cells, we are actually able to impregnate with cytokines like IL-2  or IL-15, creating that beautiful petri dish microenvironment inside the body, right? Because it worked in the petri dish, what happened? So, this really improves cell survival, persistence, and activity of the cells.

Our goal is to avoid that cytokine toxicity because we really want to make sure this therapy works where it needs to without triggering the rejection. Which brings me to the last point: Each microsphere has a robust outer shell that protects against immune attack and degradation in a tailored inner shell core that holds the therapeutic payload. We really think of ourselves as an enabler.

Gotcha. And so obviously, as an enabler, you are making your platform and methodology available to organizations that are working on the actual therapies that would be more effectively delivered by way of this encapsulation technique. So, tell us a little bit about hypothetical or real, not necessarily named, but what's a common scenario and how does that kind of partnership or licensing arrangement work to get the therapy and your platform in concert delivering something to patients?

Well, this is the heart of Likarda. Partnerships and licensing are what drive us and what allow us to amplify somebody else's innovation. So, instead of one therapy at a time, Likarda has decided our platform can impact dozens across pharma pipelines. So, partnership is very, very important to us. We really want to think about for, I don't know, biopharma partners: we are not inventing our own therapeutic payload. We are enabling a better delivery for your innovation through our encapsulation.

So, we work with manufacturers or CDMOs to provide them with an optimal formulation. Let's say, after a client has come to us, we have provided our encapsulant and they have our formulation, then really we have a tech transfer into their manufacturing facility or CDMO of their choice where they can produce it at scale. That really de-risks anything where they're not relying on our CDMO; we're not tying anybody up with a manufacturing contract. We really enable that sustainable, scalable drug delivery and providing all the tools, including the equipment, the formulation, the precursors, to the owner of the API.

And then, as you work with folks, and you work on the product or the platform internally there, are there any additional things ahead in terms of problems to be solved or challenges to be addressed, whether it's with the platform technology being developed at Likarda internally, or whether it's with accommodating formulations that are being brought to you for delivery? What else is out there on the horizon that your folks are working on to move it and advance further?

Tom, we've been doing this for a long time. So obviously, there are always going to be, I like to call, milestones on the road to the patient. So, there are certain gates that will always need to be opened. Yes, we have solved the science, and we have a lot of different pharma companies we work with. So, now it's about scaling and standardization and providing regulatory clarity.

So, to those points, maybe if we're talking about scaling manufacturing, it would be great for us to continue the journey on going from milligrams to kilograms of encapsulated materials consistently. Obviously, we want to continue to work with regulatory agencies and educate the agency on our encapsulation technology. This is new, and it's important for us to get ahead of that. So, whenever our clients incorporate us into an IND, we make sure we are part of their regulatory meetings and so forth.

We're always optimizing release profiles for different tissues or different diseases. Actually, this year we started doing something quite different — and for me, who used to work in the lab two decades ago. We implemented AI that actually is suggesting, based on our nine years of internal data and external data, what is the optimal formulation for this API, down to precursors. So, it's great to see how fast we can turn it, but also that allows us to test three or four formulations faster. So, we're constantly looking at what else we can do.

Great, great. So, I just have one last question for you, Stella, and that is one I like to end with, which is really looking out over the horizon, whether you would define that as near or far: If the advances take hold and move forward in commercialization and market penetration in the way that we would anticipate and hope, what difference do you think that might make in the patient experience, the patient landscape? Obviously, we would hope for reduction in symptoms, and, in some cases, cures. But from the patient experience of even receiving therapies, how do you think that might differ and benefit their lives and their health?

That's a great question, Tom. I mean, this is what it's all about. And the entire Likarda team and founders really all lined up. It's really about patient experience.

So, number one, fewer injections. We really want to have this lower costs [and increase] convenience, adherence, better quality-of life factors integrated into our advanced therapies.

Obviously, more durable response. So, steady disease control.

Lower side effects, and we hope we can achieve that by delivering our therapy directly, let's say to a targeted tumor, to reduce systemic toxicity. We can also apply these principles to biologics and proteins.

And honestly, greater access, simplifying logistics. I mean, we're working at delivering our technology at minus 80, so that's an ice pack to minus 20, and eventually, to room temperature. That doesn't just open up global markets, but think of those remote locations for patients. Think about lowering the cost of products to the point where you don't have to depend on liquid nitrogen transportation.

So, kind of where we started [this discussion]: Whether we're talking about diabetes or oncology or those rare conditions, maybe administration once a month — no repeated hospital visits every week —is what's going to make the patients stay on therapy.

Great. That all sounds very promising. I want to thank you, Stella, for sharing your insights on the therapeutic targets and patient needs, as well as [on] the work being done there on platform technology delivery at Likarda. And to our audience, I want to thank you for joining us for another episode of Supplier Horizons. And we'll see you next time.