Episode 4: The Science of Skin

[music] (00:09)

John Price: (00:17)
Welcome to Coffee with Kindeva, a series of thought-provoking conversations about complex drug delivery. Today, we will be talking with Laura Walsh and Tim Peterson about the science of skin and the role Kindeva technologies can play. I’m your host John Price. We are honored to have two guests today for our show. Tim Peterson is the technical manager at Kindeva Drug Delivery and Laura Walsh also with Kindeva as a business development manager. They have over 50 years of combined experience in the healthcare space. Today’s conversation will focus on delivery of drugs to, and through the skin. A two-page PDF detailing much of the discussion is available under the description to this podcast. So let’s start by talking about what makes the skin an interesting area for administration of drugs. Tim, do you want to tackle this question first?

Tim Peterson: (01:10)
Sure. Thanks, John. The skin is an interesting organ to deliver drugs through, its a protective layer, obviously it protects our body from dehydration and infection. And it turns out to be an excellent barrier and it’s a sometimes difficult barrier to deliver drugs through, but it offers the potential for avoiding some of the metabolism and drug degradation that can occur when drugs are delivered orally for example. In the case of transdermal patches, for example, that offers a chance to promote patient adherence. It’s sometimes a more convenient dosage form for patients to use. And sometimes we have a shot at improving both safety and efficacy. Sometimes the metabolism that the drugs undergo within, drugs that are delivered orally can lead to some of the side effects associated with some of those drugs. So in some cases it can actually be an optimal way to deliver drugs.

John Price: (02:18)
Okay, great. Laura, as your role as BD, do you find generally when you’re talking to somebody their knowledge that skin can be an interesting way to administer drugs or do you have to explain that to them? I’m kind of wondering what the general education is out there to, to the same question. So why the skin?

Laura Walsh: (02:43)
I think that’s a super question, John. Actually, I think the answer is no. Certainly my experience, most companies will find a drug that they think is an interesting one and decide to deliver it via the most obvious route, which is by being swallowed or taken orally. It does take a little bit of education to suggest that particularly small molecules would pass through the skin and therefore work around those side effects that Tim just referred to. Particularly with problems with side effects through the GI tract and also issues with bioavailability. So not many companies initially go straight to thinking about delivering drug through the skin. We’ve been doing it for many years, 50 years or more, and had many, many successes and kind of first in terms of inventions with respect to delivering drugs through the skin. So we’re very used to delivery drugs through the skin and certainly, you know, a raft of molecules that we have either done before or kind of could identify as being suitable for that type of delivery.

John Price: (03:59)
That’s interesting that you mentioned pills going through the GI tract. So obviously, you swallow a pill, it goes into your stomach. Does that mean that when you have a pill with the active pharmaceutical ingredient or the API, the drug in it has to have more of the API because some of that’s going to be destroyed in the GI tract where if you’re delivering through the skin, there’s potential, if you have the right molecule, you could have a lower dose of that molecule to deliver the same sort of efficacy. Is that the case? I guess Laura a question for you.

Laura Walsh: (04:33)
So yes, that could be the case, or sometimes it may be that the tablet has to be taken with a meal, let’s say so that the fact that there’s food in the stomach would help that particular drug stay longer in the stomach before passing then onto the parts of the GI. In some cases, the instructions are to take without food because actually the tablet needs to pass quickly from the stomach to another part of the GI tract. So it’s still a very tricky way to deliver drugs, even though it seems the obvious way, put it in a pill and swallow it.

John Price: (05:14)
So, Tim, I was going to ask with transdermal patches, I know some of those can stay on for not just a day, but like a week. Is there some level of control with a transdermal patch delivered through the skin that you might not find, I certainly know there are extended release tablets, but I don’t know of any that that lasts for a week. You take it once and it will dissolve over a week in your stomach. But I do think there are some patches that you can keep on for an extended period of time, more than just a day that will deliver medication throughout. Is that the case?

Tim Peterson: (05:53)
Yeah, that’s true. There are patches that deliver the active ingredient for up to seven days. There’s others that the dosing schedule is twice per week. And then there are others that are once a day or sometimes in rare cases, a little bit less than once a day. But yeah, that’s one of the benefits of delivering drugs transdermally is it is a sustained release dosage form, so we can get a relatively constant input of drug over time. Whereas when you take a drug orally, there are some extended release technologies associated with oral delivery, but it doesn’t extend over the same period of time that we can with transdermal delivery,

John Price: (06:41)
We’ve been talking about delivery through the skin. It probably is a good idea to describe the basic structure of the skin and perhaps try to describe some of the layers of the skin and the thickness of each layer. And most people think well it’s my skin. But there’s a lot going on in those layers. Tim, do you want to take a shot at maybe describing those layers for me?

Tim Peterson: (07:04)
So, at a high level, most people think about skin as being composed of three layers. One being the epidermis, that’s the outermost layer, the thicker layer underneath that is called the dermis. And then underneath that is a subcutaneous fat layer. Within the epidermis, there are actually several levels within that. The outer most layer of that is the stratum corneum. And that’s a very, very thin layer of dead skin cells. We’re constantly creating new skin cells and sloughing them off over time. And the stratum corneum provides a lot of that protective feature that we were talking about earlier, protection from water loss, protection from infection, that sort of thing. But it also provides a high barrier to drug delivery. So, it also what makes it difficult to deliver drugs through the skin. So it provides a challenge for transdermal delivery. The epidermis itself is even going deeper than the stratum corneum is very thin. Overall it’s no thicker than a sheet of paper. So, a lot of highly necessary functions for the body are present in that very thin layer that covers our entire body.

John Price: (08:25)
Laura, now I know that Kindeva offers several technologies for delivery of drugs to and through the skin. There’s a passive transdermal product such as drug in adhesive patches, as well as active transdermal products, such as solid and hollow microneedles. Describe to me some of the differences between these delivery platforms and why someone might choose one route of administration over another.

Laura Walsh: (08:49)
Maybe we go back to Tim’s description there at the stratum corneum because essentially that, I guess differentiates or allows us to take different pathways when we think about delivering drugs through the skin. So, for decades we’ve been developing products that will allow drugs to pass through the skin. So through that stratum corneum, but they move through the stratum corneum in a sort of a passive way, so that they’re only a certain size and certain other characteristics of that molecule mean that they will just naturally pass through that barrier. Going back a decade or more ago, there was a realization that delivering drugs through the skin was a super way to deliver medications and work around that GI issue that we talked about. So larger molecules, for example, such as macromolecules peptide proteins, and even vaccines could be delivered through the skin, but may be, would need some assistance to pass that stratum corneum. So, hence we developed a series of, or a platform of microneedles. So we have two types of microneedles. One is a solid microneedle, which delivers drugs to the epidermis and the drug is coated onto the very tips of those needles and applied through the Stratton cornea and delivers those to the epidermis. And then we have another series of microneedles, which are hollow, so a hollow microneedle that would deliver and do deliver liquid formulations up to two milliliters per dose, which is a huge dose to be delivered intradermally. Essentially we broadened the horizon, or we widened the scope for delivery of molecules through the skin from small molecules and the passive patch to much larger molecules with the assistance of microneedles into proteins, peptides, antibodies.

John Price: (10:56)
Tim, anything to add to that?

Tim Peterson: (10:57)
Just one other thing regarding the microneedle systems and also the structure of the skin. So within the skin itself, there are immune responsive cells. They’re like Langerhancells that can actually initiate an immune response. So it’s a great target for delivery of vaccines as well. And that’s one of the areas that our microneedle platform can access.

John Price: (11:23)
Now we are attaching the science of skin brochure to this podcast it’ll be available. But I see on there that we’ve got a new product we are currently developing, the gel patch. Describe to me how this works and how it’s different than a traditional transdermal patch. Tim, why don’t you give a shot at that?

Tim Peterson: (11:45)
This is a technology that is basically applied like a gel. There’s an applicator that allows the gel to be applied at certain thickness and over a defined surface area. And then within a period of a couple of minutes that gel material dries to a film basically forms something close to a transdermal patch in place. It can be worn up to up to a week like other patches, and then removed intact like a transdermal patch. So it has very good adhesion to unusual areas of the skin like joints and irregular surfaces, and also has the ability to be applied to wound areas as well. So we look at it as a very nice addition to our transdermal portfolio. Potentially accesses some therapies our current technologies don’t address.

John Price:
Laura anything to add to that about the gel patch?

Laura Walsh: (12:48)
Well you mentioned before that I’m a business development person, and I am exceptionally excited about this gel patch technology, because I’ve spoken to customers over the years who understand how super a transdermal patch can be, but then have patients who have issues with the parts of the body that don’t really lend themselves to attaching patches or plasters or indeed anything that is relatively rigid. So, you think about a patient who might have issues with painful diabetic neuropathy, so issues with pain in the ankles, or patients who have issues with sore knuckles. So this is because it’s flexible, it’s waterproof, it creates a barrier maybe for somebody who has a skin complaint that they may be embarrassed about. So I think in terms of the patient experience, I think in terms of being able to deliver drugs to parts of the body that are non-uniform it presents itself as a real game changer, in my opinion.

John Price: (13:54)
I look forward to hearing more about this new product. With that in mind, I know some of these delivery technologies have been around for years while others, like the gel patch are brand new. Give me an idea of where these different delivery platforms are in terms of development and commercialization. Laura, why don’t you tackle that one first?

Laura Walsh: (14:17)
Yeah. So this is really exciting. So for the solid system, a year has gone by, so this time last year we entered a phase three with Radius Health Care so that’s in the public domain. Look that up and read that if you’d like to. Alongside that and in parallel to that, we’ve been scaling up for some time to commercialize that platform. You look around, you cast your eyes around to other microneedle companies and many have advantages and disadvantages, don’t we all, but where we think we are particularly outstanding is our manufacturing capabilities. And, we are, I think best in class when it comes to scalability and for this type of tricky technology. And then thinking about the hollow microneedle system, so this is the system for injecting liquids, we have been in the clinic with partners for a cancer immunotherapy programs. So they’ve gone super well, that’s very exciting and intriguing. And indeed we are in phase one with the hollow microneedle technology.

John Price: (15:33)
So just a brief clarification. I think you said the solid microneedle this time last year, it was actually 2019. So this time two years ago we went into the trials there. So, maybe with the gel patch, I know that’s brand new. And you know, we’re really just coming out with that, but I’m guessing from a technical standpoint, there’s a number of things we test and get ready for before that. Maybe talk to me a little bit about what some of the work we’ve done with gel patch to date.

Tim Peterson: (16:06)
I think one of the things that we do with all of our transdermal drugs are we assess delivery on an in vitro basis. So, we looked at delivery of actives from the gel patch technology on an in vitro basis. We’ve done that with a number of molecules. With that platform we’ve also done some work to evaluate the safety and tolerability. We’ve done some clinical work without the active presence. So although I’d still consider this in preclinical stage, it is ready to move forward with new actives that our partners may consider for this platform and move quickly into the clinic.

John Price: (16:53)
Laura, what do you see is maybe the important applications for some of this gel patch technology?

Speaker 4: (16:58)
I think there are multiple applications. So, at the moment we do see a great leap for dermatology. So, diseases of the skin, rather than perhaps delivering drugs through the skin. So psoriasis, eczema, particularly because these types of complaints let’s call them, are never uniform. Psoriasis can be different depths, different shapes. It can be on the hands, it can be pretty much anywhere on the body. We also think wound care could be an interesting area because, and Tim can help here, we have looked at the gel patch applicability for intact and non-intact skin. So wound care again, could be a really interesting area, particularly because an API would be incorporated. That could be again, another game changer scenario.

(18:02)
John Price: Great. Tim, anything to add on that?

Tim Peterson: (18:04)
I think Laura brings up a great point. One thing in dermatologics and also in the wound care area, one aspect of a transdermal gel patch is that it provides protection of the site as well. So some of those conditions patients may feel an urge to itch, for example, or you just want to protect the site and with the gel patch technology, it’s possible to do that.

John Price: (18:32)
Moving on. What are some of, so Laura this is really for you here, what are some of the factors that drug manufacturers should consider when selecting a CDMO or a contract development manufacturing organization, and how does Kindeva stand apart from other CDMOs?

Laura Walsh: (18:50)
If I would kind of put my finger on exactly why I think the experience or know the experience that we have within the organization is superior to other CDMOs, we focus with laser precision on two areas, which is delivering drugs to the lungs and to the nose, but also through the skin. So that’s where we operate. We don’t operate any other areas. We’re experts that we have people within the organization who have decades of knowledge and experience to bring, to bear we’d love to solve problems, bring us a problem. That’s where we are at our best. And, I think compared to the CDMOs who may spread themselves more widely, perhaps thinner come to us, we know exactly what we’re doing in those two areas. And we’ve got a track record that proves that to be so.

John Price: (19:48)
Tim, anything to add? I know, we’ve talked about this before on some of the other podcasts, but Kindeva is a new name in the industry, but we’ve certainly got a track record that goes back 50 plus years, and we’ve got people with experience decades back. So do you want to talk about that maybe a little bit in your role?

Tim Peterson: (20:09)
We are fortunate to have many, many people within our organization that have a long history of working in drug delivery and in products for delivery of drugs through skin. We have a heritage back through 3M before we were Kindeva. And, even going back before that with Riker Laboratories and early work on inhalation products. So we’ve been present in the transdermal business since its inception. So we worked with some of the companies that were the very first transdermal products. And we went on to develop our own formulation and manufacturing capabilities for transdermal products. So a really strong background in the transdermal area. And we continue to build on it all the time.

John Price: (21:03)
This last question here is actually going to be for both of you, but let’s start with Laura. Within the timeline of a company’s development, when is the ideal time for them to start working with a CDMO and why?

Laura Walsh: (21:17)
The earlier the better. And that’s because the way we work is we have due to our experience, but also some preparatory and models, empirical models, that we have within the organization. We can fairly quickly say to an organization that a molecule will or will not be suitable for delivery through the skin, or indeed we’ve spoken about the lungs, we’re here to talk about the skin, but we can very rapidly say, this is a candidate, this is on the edge, but we should give it a go or this is not going to work. And we like to get there quickly that’s the way we operate. So the sooner an organization comes to us, the better. We can always bridge later down the line in development. And indeed we have done that and do do that in different phases of development, but it’s almost certainly better to identify the best route of administration as early as possible.

John Price: (22:16)
That makes sense, Tim, I’m assuming you’d agree with that, anything to add?

Tim Peterson: (22:21)
I think I would agree with what Laura said. It’s nice to work with companies and we have worked with a lot of companies that have new drugs that they see an opportunity in transdermal delivery, and we’ve worked on a number of new chemical entities and that’s sort of on the front end of development. But we do offer our manufacturing services, for example, to companies that might be looking for a manufacturer of an existing product. And we operate in the full continuum between those two things. So, we see partners come to us that may have developed their own formulation and need to go through the rest of the development process. And we scale those products up for them, just basically we can work with companies wherever they’re at within the development continuum.

John Price: (23:15)
I really appreciate both your time today. I appreciate the insights into the science of skin. As I mentioned earlier, that brochure will be available in the description to this podcast. Thank you both very much for your time.

Tim Peterson: (23:31)
Thank you, John. Thanks, Laura.

Laura Walsh: (23:33)
Thanks. Thanks Tim. Thanks John.

John Price: (23:43)
Thank you for listening to Coffee with Kindeva. A series of thought-provoking conversations about complex drug delivery. Join us next time as we continue the journey into the fascinating world of Kindeva Drug Delivery.