Localized Treatments Via Precision Injections With RheoTek's Dan Mazzaferro

Dr. Daniel Mazzaferro, founder and president at precision drug delivery technology company RheoTek Medical, joins Supplier Horizons host Tom von Gunden in a discussion of using needle-based and needle-free injection systems for precision targeting of skin cancers and other dermatological indications. The conversation includes coverage of the goals and benefits of localized rather than systemic approaches to therapeutic administration and mechanisms of action. 

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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. Dan Mazzaferro, who is founder and president at RheoTek Medical, a precision drug delivery technology company.

Welcome, Dan.

Dan Mazzaferro, Founder and President, RheoTek Medical

Hey, great to be here. Thanks so much for the invite. I'm excited to dive into this.

Excellent. Well, it's my privilege to have you here. Thanks for joining. So, I know that you're working on injection systems — precision injection systems — both with needles and needle-free. So, before we get into the technology, I know that a major thrust of the approach is to deliver localized treatments rather than systemic ones. So, let's start at that high level. What are the goals and benefits of localized versus systemic treatments?

Yeah, great question. I think this is really where the future of medicine is going, especially for tumors all over your body. Tumors in organs all over your body, whether we're talking about your largest organ being your skin, to areas in your brain, to areas in your heart, to your lungs, to your bladder, to your colon, and it goes on.

And so, by being able to deliver something locally to where the actual area of concern is, whether it is a biopsy you need or if it's a tumor, like a type of a cancer that you need to treat, precision in reaching that area is critical. And especially if you're delivering something to that area, that tumor that exists, then you want to be able to make sure you're delivering it specifically to that area. And the reason the interest in doing this is because you're only targeting that one specific area of that organ.

So, for example, if you have a skin cancer on your face and you deliver something specifically to that one area, then only that area is really being affected. So, if you wanted to do immunotherapy or some oncolytic virus, rather than having to deliver it as a bolus injection or an infusion so your entire body is being consumed by this type of a medication, you can deliver it locally to this area so you don't have to worry about systemic adverse reactions. Systemic meaning full body reactions because it's really just targeting that one area. What's also important, though, is you need this precision of the delivery system to make sure that you're not wasting product. It's not going to the wrong area.

And also by doing it in that specific targeted area, it has a possibility of also generating some immune response. So, it remembers it for the future. So, a lot of exciting things. And for those patients that are transplant patients at higher risk of getting these types of very potent medications where you want to decrease those systemic reactions, those systemic effects. And so, a lot of excitement about where personalized medicine via localized delivery for these types of medications is going.

Good, good. Yeah. Maybe give us a little bit more of an illustration of some of these indications that you're targeting. I heard you mentioned skin, obviously you were mentioning tumors. So, what are some of the initial front-of-mind treatment areas for you folks?

Yeah. So at RheoTek Medical, we're focusing mostly on the skin. And that could be anywhere on the body: face, head, chest, back, anywhere. And as you briefly mentioned before, a needle system and a needle-free system. We'll get into the specifics of those. And so, what we are really focused on, both chronic conditions and cancers. And then there's obviously some ...

I was just going to say, how would things typically be given to these patients today ahead of these systems that you're working on?

Yeah, great question. So, if you look at skin cancer, for example, a basal cell cancer, a squamous cell cancer, or a melanoma. Those are the three most common types of skin cancers. A lot of times if they're on sensitive areas like the face, then you would have Mohs [surgery]. Some people are not familiar with that, but it's a way of removing the skin cancer with the least amount of extra tissue. Other surgical oncologists would remove it cervically on your body, your chest, or your back. And then, if it was very advanced, you may also need some sort of immunotherapy, and this could be an infusion. So, every week, you have to go to an infusion center, you have to get this large bolus infused via IV. And there's some interest in doing large bolus injections into subcutaneous fat — bolus means large volume —injections as a way to circumvent or avoid doing infusions.

And so, that results in a systemic reaction. It’s going into your systemic blood, especially infusions, going directly to your bloodstream to have a systemic effect. So, you can have a lot of side effects with this versus having it be localized.

Gotcha. If you had a thought that I interrupted there when I asked that question, feel free to continue it.

Yeah, my only thought is, this is where we're focusing our efforts on. But I have to give a shout-out to what I know some other companies are looking at too. And that is using an endoscope, so a camera, whether it's going from the top down or the bottom up and using cameras and some very, very unique technical robots and gadgets to be able to deliver some localized immunotherapies or other oncology type medications directly into tumors, whether it's the colon or if it's the stomach. And so, it's a lot of exciting things. And it's all about making sure you're delivering in the right area precisely to where it's needed.

Yeah, yeah. Let's talk about the technology. I think probably start with precision needles and then move on to needle-free. So, what does it mean to add the word precision to needle? What actually happens when you do that?

Yeah, great question. So, everyone's like, you have this very small needle. Don't we have good physicians and injectors that could inject? At the same time, I just heard another video of Elon Musk a week or two ago saying that, in three years, his robots are going to be better than the best surgeons out there. And so, when we talk about precision, robotics precision, then there is clearly a difference from what the human hand can deliver versus what robotics can deliver or some technical hardware can deliver.

For example, our device can do sub 0.1 millimeter precision of where the needle's going. And I mean, right now we're talking like this [demonstrates with his hand], that difference between those two fingers is one centimeter or 10 millimeters. And so, when we talk about sub-0.1, I can't even go small enough to show you how precise 0.1 millimeters is.

And that's what is able to be controlled with a device like ours versus with my human hand. I can't control that with my hand when doing: even one millimeter of level of control is extremely challenging. And that's why, when you look at the thickness of the skin; the epidermis is less than one millimeter. I mean, we're talking, it's usually around 0.2 or 0.3 millimeters, the epidermis, the top layer of the skin, then the next layer of the skin is the dermis, and the dermis can range from one millimeter to about three or four millimeters. Even the dermis is that thin. So, in order to get something precisely delivered in there, you really need to have some precision tools or techniques to be able to get into the area. Otherwise, you're going too deep into the fat, and it's not going to have the right targeted effect, or it's made too superficial and then the product is wasted and it's coming out the skin.

Gotcha. Yeah. So, it sounds to me like there's got to be some sort of preset that you're measuring the distance or something like that to make sure it lands exactly where it's supposed to land, so to speak.

Yeah. So, we have a way of controlling the device relative to the skin. And then we also have just fine-tuned control as to where the needle is moving in relation to the device. And then you have to also be mindful on this too, because if you're using traditional needles and you're going directly perpendicular the skin and you inject like that, then the product usually goes deeper than where the actual needle is. And so, we have some clever ways of being able to utilize different tools and techniques to be able to maintain it within the actual superficial layer of the skin. And that's the nice thing about the needle. I mean, if you want, I can also give you a quick highlight of the needle-free and the precision of needle-free.

That's exactly where I was going next. Tell us about the ... I mean, obviously the difference is one does not have a needle. So, tell us a little bit about that.

Yeah, so needle-free is ... I almost think of it as a power washer on the side of the house where you're just like, it's very, very, very high-power pressure water that's being injected out, but on a significantly miniaturized version and scale of that. And so really, we use an electromechanical type of system to be able to generate this power. It actually requires a lot of stored energy in order to release this stored energy to be able to exert the kind of force that's needed. I mean, the water's being pushed out about a third the speed of sound, so it's very quickly, which we can get into later on, the questions about the effects on molecules and which ones. But again, we use electromechanical systems. The two other systems that are out there in the market right now is one, some people use springs, and the other, people use pneumatic systems.

And so, we found, in order for us to do multiple rounds of injections and at variable volume, variable depth, we have found it best to be able to use an electromechanical system. And what we've also found is that a needle-free system does not have the precision that you can have with a needle. But it does allow a much wider dispersion when you're delivering it.

And so, there are some values and some considerations in that because it can increase the immune response. If you're injecting something higher power, higher pressure, and it exerts a wider dispersion, then you have a wider surface area that the antigen-presenting cells or the immune cells that your body has can respond to this liquid that was just delivered. And then your body can increase an immune response relative to what's delivered.

So, they really have different indications as to really what you're trying to go after, which is why we found it very important, to be a precision drug delivery technology company to really have both of these in our wheelhouse.

Gotcha. Well, I'm going to conclude our conversation, Dan, with a place where I like to conclude these, and that is actually out into the landscape of the patients themselves. A landscape, I know that you know well and will probably be back to as a practicing physician within moments of ending this conversation with me. So, as you look out into the potential future state and the lives and health and experiences of patients, if these advancements move forward and take hold, how do you imagine that to be different for them?

Yeah, it's funny, being a surgeon, I would love to say I would love to continue to operate. As I mentioned before, Elon Musk has robots going to take over all physician jobs. We'll see. But I would also love to see the future where we don't have to be cutting out skin cancer. That is a goal that I hope to be a part of the future of this landscape, because there are millions of people that are being affected by skin cancer every single year. And, therefore, there are also millions of people that are having ... Well, even if it's a few millimeter tumor or it's a few centimeter tumor, when you cut those out and you have to do the reconstruction, the reconstruction is often two, three, four times the size of what you're needing to do in order to reconstruct. And so, being able to avoid having to create a huge scar and a huge reconstruction on someone's face or any part of the body, it would be, I think, a tremendous success in our medical field if we are able to in the future.

And then in the not-too-distant future, be able to directly inject immunotherapies into the tumor itself, have the tumor recede and not have to worry about creating a large defect and a large scar over someone's entire face.

Yeah. That does sound tremendous and also promising. So, Dan, I want to thank you for joining me for this episode. And I also want to thank our audience for joining for another episode of Supplier Horizons. And we'll see you next time.