Latest / The Science of Skin / Roflumilast vs. Crisaborole: The PDE4 Science That Changes Everything

Transcript

Roflumilast vs. Crisaborole: The PDE4 Science That Changes Everything · The Science of Skin

• 0:00
  SPEAKER_00: Thank you to our sponsor, Arcutis Biotherapeutics, for their support of the Science of Skin podcast and furthering Derm Education.
• 0:07
  SPEAKER_00: Arcutis is a medical dermatology company that champions meaningful innovation to address the urgent needs of individuals living with immune-mediated dermatological diseases and conditions.
• 0:18
  SPEAKER_00: With a commitment to solving the most persistent patient challenges in dermatology, Arcutis has a growing portfolio of advanced targeted topicals.
• 0:27
  SPEAKER_00: Arcutis's unique dermatology development platform, coupled with their dermatology expertise, allows them to develop differentiated therapies against biologically validated targets for a range of inflammatory dermatological conditions.
• 0:41
  SPEAKER_00: Arcutis strives to simplify disease management and optimize drug efficacy, safety, and tolerability.
• 0:48
  SPEAKER_00: They're determined to elevate the current standard of care, solving for the challenges others haven't.
• 1:02
  SPEAKER_01: Hello and welcome to the Science of Skin Podcast.
• 1:04
  SPEAKER_01: My name is Dr.
• 1:05
  SPEAKER_01: Ted Lane.
• 1:06
  SPEAKER_01: I'm a board certified dermatologist in Austin, Texas, and your host for today.
• 1:09
  SPEAKER_01: Hey, while I have your attention, thank you so much for listening.
• 1:12
  SPEAKER_01: If you don't mind, give us a five-star rating and subscribe.
• 1:15
  SPEAKER_01: We love our subscribers, and I promise you we're gonna give you great information every week.
• 1:20
  SPEAKER_01: And it is my pleasure.
• 1:22
  SPEAKER_01: Speaking of great info and great guests, it's my pleasure to introduce Dr.
• 1:26
  SPEAKER_01: Chris Bunich.
• 1:27
  SPEAKER_01: Dr.
• 1:27
  SPEAKER_01: Bunich is an associate professor of dermatology at the Yale School of Medicine.
• 1:32
  SPEAKER_01: He also runs the Bunich Lab at Yale.
• 1:35
  SPEAKER_01: He's the editor-in-chief of Dermatology Times.
• 1:38
  SPEAKER_01: And finally, Dr.
• 1:38
  SPEAKER_01: Bunich has his own amazing podcast called The ABCs in Dermatology.
• 1:43
  SPEAKER_01: We'll all have to check that out.
• 1:45
  SPEAKER_01: Chris, thank you so much for joining us.
• 1:47
  SPEAKER_02: Ted, it's a pleasure to be here.
• 1:48
  SPEAKER_02: Thanks for having me.
• 1:49
  SPEAKER_02: And I can't wait to talk some science and skin with you.
• 1:53
  SPEAKER_01: Yeah, hey, thanks.
• 1:54
  SPEAKER_01: So we are talking today about Zareve, right?
• 1:58
  SPEAKER_01: Which is Reflumolast.
• 1:59
  SPEAKER_01: It's formulated in both the cream and foam.
• 2:02
  SPEAKER_01: And I should say this episode is being sponsored by Arcutus, which makes Reflumolast.
• 2:07
  SPEAKER_01: And Chris, you you in particular, I'm so excited to have you on because you've done so much research into these PD4 inhibitors and really looking at the differences and similarities between them.
• 2:19
  SPEAKER_01: Maybe we should start off with that.
• 2:21
  SPEAKER_01: And why you think reflumolast really should be really a product of choice for atopic dermatitis and even psoriasis?
• 2:29
  SPEAKER_02: Well, Ted, a lot of that research started from a very simple, simple clinical question.
• 2:34
  SPEAKER_02: And that was, well, we've been using chrysoborol for a while and atopic dermatitis.
• 2:40
  SPEAKER_02: I don't think people were overly overwhelmed with the efficacy of the product.
• 2:45
  SPEAKER_02: And there was a lot of the burning and stinging our patients suffered.
• 2:49
  SPEAKER_02: And when reflumalast came to the market, the question really was, how is this any different from our experience from chrysoboral?
• 2:57
  SPEAKER_02: And we approached this initially from a scientific angle where we just asked, what are what's the different biochemistry of how reflumolast binds to PDE4 compared to chrysoborol and also a premolast.
• 3:12
  SPEAKER_02: And it gave us some really, really interesting insights into how PDE4 works, how cyclic AMP works, and then obviously how the PDE4 inhibitors work.
• 3:24
  SPEAKER_02: And to summarize that in a nutshell, Ted, it's what we found was that reflumolast mimics the way the natural substrate, cyclic AMP, how cyclic AMP binds to PDE4.
• 3:37
  SPEAKER_02: Reflumolast mimics that cyclic AMP binding better than a primolast and chrysoborol.
• 3:43
  SPEAKER_02: And when I say it mimics it better, it has three key anchor points in the PDE4 enzyme, which is a is really a hydrolase, right?
• 3:52
  SPEAKER_02: It uses water to break apart cyclic AMP.
• 3:55
  SPEAKER_02: A primolast only had two anchor points.
• 3:57
  SPEAKER_02: Chrysoboral only had one anchor point.
• 4:00
  SPEAKER_02: So what does all that mean clinically for us as dermatologists?
• 4:03
  SPEAKER_02: Well, what it means is that reflumolast actually has a really, really high binding affinity to PDE4 compared to a premolast.
• 4:13
  SPEAKER_02: It's actually two fun, two hundredfold more potent at inhibiting PDE4 than a premolast.
• 4:19
  SPEAKER_02: And it's actually over a thousandfold more potent than chrysoborol.
• 4:23
  SPEAKER_02: And when we were able to connect this biochemistry to clinically important potency differences, it started to be clear to me as a clinician that reflumolast is different.
• 4:35
  SPEAKER_02: It's not just another PDE4, it's a very unique medicine within the PDE4 inhibitor family.
• 4:42
  SPEAKER_02: And that gave me the confidence personally to use it in my patients.
• 4:46
  SPEAKER_02: Because what it does is it sort of activates anti-inflammatory pathways.
• 4:52
  SPEAKER_02: When you hydrolyze cyclic AMP to the kind of monophosphate, right?
• 4:59
  SPEAKER_02: What you're seeing there is increase in inflammation, increase in driving of inflammatory pathways.
• 5:06
  SPEAKER_02: That's why inhibiting PDE4 is helpful, it protects the cyclic AMP from hydrolysis, so that cyclic AMP can drive anti-inflammatory transcription programs.
• 5:18
  SPEAKER_02: Whereas the monophosphate, adenosine monophosphate, that actually will then drive more inflammation.
• 5:25
  SPEAKER_01: So by increasing the levels of cyclic AMP, we're able to reduce the expression of pro-inflammatory cytokines and increase anti-inflammatory cytokines like IL-10, for example, correct?
• 5:36
  SPEAKER_02: That is great.
• 5:37
  SPEAKER_02: And actually, you raise a really good point, Ted.
• 5:39
  SPEAKER_02: The type of cytokines that are being suppressed, it's really important because it's not just one or two cytokines.
• 5:48
  SPEAKER_02: What targeting PDE4 can do, it's upstream of the pathways that we normally think about, say in atopic dermatitis, for example, or psoriasis.
• 5:59
  SPEAKER_02: PD4 is upstream and it's responsible.
• 6:02
  SPEAKER_02: Uh cyclic AMP uh hydrolysis can actually lead to activation of type 1, type 2, type 3 cytokines.
• 6:11
  SPEAKER_02: So this would include your TH1, like interferon gamma, TNF alpha, TH2, IL4, IL13, and TH17, TH22 cytokines.
• 6:21
  SPEAKER_02: It can actually regulate and lead to upright uh increases in all those cytokines.
• 6:26
  SPEAKER_02: And we want to control that.
• 6:28
  SPEAKER_02: And that's what PDE4 inhibitors do.
• 6:30
  SPEAKER_02: And when we think about the contrast to JAC inhibitors, JAC inhibitors are way downstream inside the cell, controlling the intracellular signaling from those cytokines.
• 6:43
  SPEAKER_02: PDE4 is way upstream of those cytokines, and you're trying to prevent their formation in the first place.
• 6:50
  SPEAKER_02: In a way, I view PDE4 inhibition as a comprehensive approach to downregulating multiple cytokine pathways, inflammatory pathways.
• 7:01
  SPEAKER_02: And it's sort of the opposite end of the spectrum of where we think about Jack inhibitors.
• 7:10
  SPEAKER_00: Thank you to our sponsor, Arcutis Biotherapeutics, for their support of the Science of Skin Podcast and furthering Durham Education.
• 7:18
  SPEAKER_00: Arcutis is a medical dermatology company that champions meaningful innovation to address the urgent needs of individuals living with immune-mediated dermatological diseases and conditions.
• 7:29
  SPEAKER_00: With a commitment to solving the most persistent patient challenges in dermatology, Arcutis has a growing portfolio of advanced targeted topicals.
• 7:37
  SPEAKER_00: Arcutis's unique dermatology development platform, coupled with their dermatology expertise, allows them to develop differentiated therapies against biologically validated targets for a range of inflammatory dermatological conditions.
• 7:51
  SPEAKER_00: Arcutis strives to simplify disease management and optimize drug efficacy, safety, and tolerability.
• 7:59
  SPEAKER_00: They're determined to elevate the current standard of care, solving for the challenges others haven't.
• 8:06
  SPEAKER_01: Chris, it's so timely that we're talking about this because I think just today in JAD, there's an article by Gutman, uh, Dr.
• 8:13
  SPEAKER_01: Gutman and uh her colleagues regarding the kind of the cytokine and the immunologic signature of atopic dermatitis.
• 8:24
  SPEAKER_01: And while we like to, you know, group things as TH1 versus TH2, she she and her colleagues make a really good point in this article regarding, you know, it's you really can't do that because there are subsets of patients which have, for example, AD that has more of a TH1 cytokine profile.
• 8:40
  SPEAKER_01: Uh, Asian, she talks about.
• 8:41
  SPEAKER_01: Maybe uh people who are a little bit older uh have a more TH1 cytokine profile.
• 8:47
  SPEAKER_01: And so it's all a blend, isn't it?
• 8:49
  SPEAKER_01: Even when we're talking about atopic dermatitis, which we've really kind of focused on TH2 cytokine profiles, it's such a blend.
• 8:55
  SPEAKER_01: And so to have something, you know, less specific, more kind of higher up in the pathway makes a lot of sense as we learn more and more about the cytokine profiles of these inflammatory diseases.
• 9:08
  SPEAKER_02: I agree completely, Ted.
• 9:09
  SPEAKER_02: And the thing is that we think about AD as a heterogeneous disease now.
• 9:14
  SPEAKER_02: And the real the reality is there's overlap transcriptionally of genes between atopic dermatitis, severate dermatitis, and psoriasis.
• 9:24
  SPEAKER_02: There's obviously unique genes as well.
• 9:26
  SPEAKER_02: But the key point here is they're all heterogeneous to some level, and different patients will have different ratios of these cytokines to each other.
• 9:35
  SPEAKER_02: Now, you mentioned type 1 or TH1 cytokines a second ago, and I want to point out a really, really important connection that's relevant to reflumolastin PD4 inhibition, and that is interferon gamma.
• 9:49
  SPEAKER_02: And a number of diseases, including in transcriptional studies of sebarraic dermatitis, showing that there's upregulation of TH1, TH22, TH17 cytokines.
• 10:02
  SPEAKER_02: One of those TH1 cytokines is interferon gamma.
• 10:05
  SPEAKER_02: And a lot of people may not realize that one of the cosmetic or skin barrier connections of interferon gamma is too much interferon gamma downregulates ceramide synthase.
• 10:17
  SPEAKER_02: You end up having less ceramides, some of the good lipids that we need for barrier integrity.
• 10:23
  SPEAKER_02: Therefore, if you're not inhibiting, uh if you're not inhibiting interferon gamma, you're actually allowing barrier integrity, barrier disruption to continue by having decreased ceramides.
• 10:36
  SPEAKER_02: And where this connects into formulation, Ted, is actually the emulsifiers that were used in the preparation of reflumolast uh cream and foam.
• 10:47
  SPEAKER_02: And what was really unique about the formulation of reflumolast, whether it was the cream or the foam, is the emulsifier that was used in it.
• 10:56
  SPEAKER_02: It was specifically a technology, Crotofos.
• 11:00
  SPEAKER_02: And what emulsifiers do for our audience is they really allow uh different un typically unmixable ingredients to actually mix properly.
• 11:11
  SPEAKER_02: And where this comes into play with creams and foams is water and oil, right?
• 11:19
  SPEAKER_02: We know that the cream of reflumolas has 48% water, the foam 65% water, but you have to mix water and oil to have an ultimately a good product here.
• 11:29
  SPEAKER_02: And that's where the choice of this Crotofos, specifically using what are called Ceterit 10 phosphate, seterophosphate, those specific phosphates have what is called a high craft temperature.
• 11:45
  SPEAKER_02: And when I say craft, I don't mean the mayonnaise, I don't mean the ketchup, I don't mean the owner of the New England Patriots, but there's a specific, there's a specific temperature at which these emulsifiers can form micells, right?
• 12:01
  SPEAKER_02: A number of people in our audience may have used some micellar water in the past as some of their cosmetic routine.
• 12:08
  SPEAKER_02: But this craft temperature tells us at what temperature these emulsifiers form micells.
• 12:14
  SPEAKER_02: And if you form micells at too low of a temperature, say 37 degrees, like body temperature, skin temperature, it can extract more ceramides, it can extract more lipids.
• 12:26
  SPEAKER_02: And then imagine in sebrate dermatitis, you have a disease where there's already too much interferon gamma, you have lower ceramide synthase, and now you're stripping more ceramides because if you had a poor emulsifier.
• 12:40
  SPEAKER_02: So the choice of formulation for reflumolast was incredibly important because by going with this particular emulsifier, it's actually protecting its non-ceramide stripping.
• 12:51
  SPEAKER_02: It's not adding to the natural underlying disease burden from the actual cytokines themselves.
• 12:59
  SPEAKER_02: This is actually going to reduce the epidermal lipid extraction and it's also going to prevent skin irritation, particularly the burning and stinging that can come from some of this lipid extraction when you have a mismatched emulsifier.
• 13:15
  SPEAKER_02: And I think that this particular science is really relevant when we think about cosmetic elegance, we think about the feeling and the look of our skin.
• 13:25
  SPEAKER_02: The proper emulsifier choice can make a big difference by promoting barrier integrity, reducing that unwanted sensation of burning, stinging, and itch.
• 13:36
  SPEAKER_02: And Ted, that's reflected in the clinical trials.
• 13:39
  SPEAKER_02: Whether it was psoriasis, atopic dermatitis, or sebarate dermatitis, whether it was the scalp or the body.
• 13:46
  SPEAKER_02: The reality is that this was a highly, highly tolerable product, and patients favorably view it because of that tolerability.
• 13:55
  SPEAKER_02: And I think it all comes back to the underlying science that went into this product.
• 14:00
  SPEAKER_01: Chris, that was just perfect.
• 14:02
  SPEAKER_01: Thank you for that.
• 14:03
  SPEAKER_01: Um, I'm glad we have that recorded so everybody can listen to that.
• 14:06
  SPEAKER_01: You may want to listen to that again because the science behind this product and the use of Crotofoss, which historically has been utilized in the cosmetic industry as a beneficial emulsifier.
• 14:17
  SPEAKER_01: Like just as you said, the last thing you want, guys, is for us to impact that brick and mortar structure of the barrier, right?
• 14:24
  SPEAKER_01: What is the core reason for the skin is to act as a barrier, right?
• 14:29
  SPEAKER_01: When you get down to it, the skin has to be a barrier, keeps out the environment, keeps in what we need, especially hydration.
• 14:36
  SPEAKER_01: So without the barrier, our skin loses its primary function.
• 14:40
  SPEAKER_01: Anything that we do to impair the barrier, in addition to an inflammatory skin disease such as atopic traumatitis epiderm or psoriasis, uh, could worsen the signs and symptoms of that disease.
• 14:51
  SPEAKER_01: And like Dr.
• 14:52
  SPEAKER_01: Bunick said, when you look at the clinical trial data in all three disease states in which this product is approved, uh, you're looking at adverse events that are like 3% for headache, for example, have nothing to do with local skin reactions at all, quite frankly.
• 15:08
  SPEAKER_01: And so it just was so smart of David Osborne and his peers who helped formulate this to really focus on a more cosmetic application, excuse me, a more cosmetic emulsifier to be used with a pretty difficult ingredient, which is reflumolast, right?
• 15:26
  SPEAKER_02: Yeah.
• 15:26
  SPEAKER_02: And Ted, there's one other aspect of the formulation that has always meant something deeply to me, and that is the formulation at pH 5.5.
• 15:36
  SPEAKER_02: I think sometimes that we forget that our skin is acidic in nature, right?
• 15:41
  SPEAKER_02: The outside of this, the outside of the epidermis is an acidic environment.
• 15:46
  SPEAKER_02: And when you in my own lab, for those that don't know, some of the science that I've studied is actually looking at the biochemistry and the structure and function of keratins one and 10 and phalagrine, which is known as a filament aggregating protein.
• 16:02
  SPEAKER_02: That's where phalagrin comes from.
• 16:04
  SPEAKER_02: And part of its job is to help form that outer, that protinaceous component of the skin barrier that mixes with the lipids and the ceramides.
• 16:13
  SPEAKER_02: And what happens is in our own lab, Ted, we have seen that when you raise that P that pH, right?
• 16:20
  SPEAKER_02: You have a pH that heads towards seven, it disrupts the ability for phalagrin to actually properly aggregate the keratin filaments.
• 16:29
  SPEAKER_02: And if you have a product, whether it's at the emulsifier step or other aspects of the ingredients, the incipients, if you mismatch the pH, you're actually going to hurt the skin barrier.
• 16:42
  SPEAKER_02: So here, not only is there the smart emulsifier, the elevated craft temperature, so you're not forming micells with your surfactants there.
• 16:50
  SPEAKER_02: And that is really beneficial to the ceramides, but so is maintaining the pH 5.5, because that is not damaging the protonaceous component of the skin barrier, the keratin, phalagrin, and other cornified cell envelope proteins that are really critical to that skin barrier integrity.
• 17:09
  SPEAKER_01: Such a good point, Chris.
• 17:11
  SPEAKER_01: Um, phalagrin is so important, as you mentioned.
• 17:14
  SPEAKER_01: It's also in many atopics, phalagrin, there may be a genetic mutation in phalagrin as well.
• 17:19
  SPEAKER_01: So it's an altered protein to begin with.
• 17:21
  SPEAKER_01: The breakdown products of phalagrin are included in the natural moisturizing factor, which is so important to keep those dead cells, the chordiocytes, plump with hydration.
• 17:31
  SPEAKER_01: So phalagrin, the importance of phalagrine cannot be understated.
• 17:35
  SPEAKER_01: And then, of course, as you mentioned, as you raise the pH of the skin, you inhibit a very important enzyme called beta-glucoserebrosidase, which is responsible for ceramide production.
• 17:46
  SPEAKER_01: And so there's so many reasons to not only impact the to stop the impact the uh effect on the brick and mortar structure in regards to the lipid bilayer.
• 17:59
  SPEAKER_01: So you stop those surfactants from affecting the lipid bilayer, but then you also, as you mentioned, Chris, keep that acid mantle so you optimize the environment for the keratinocytes and and the the betoglucro cerebrosidase to to perform efficiently.
• 18:13
  SPEAKER_01: So I completely agree, Chris.
• 18:15
  SPEAKER_01: It's it's an amazing formulation and really meant for all three of these inflammatory uh skin diseases.
• 18:22
  SPEAKER_01: And what's impressive to me also, Chris, is if we can just turn to the foam, how well that foam works for both sebderm and psoriasis.
• 18:30
  SPEAKER_01: Um, it's on the scalp, the way that they formulated that foam, I don't know if you if you don't mind touching on that because it's really important, especially for textured hair.
• 18:41
  SPEAKER_02: Well, I think that in the case of the foam, I think that for me personally, I actually demonstrate the foam.
• 18:48
  SPEAKER_02: I use the uh the samples, not obviously not samples of the drug, but the the just the vehicle.
• 18:55
  SPEAKER_02: And I actually show my patients how to dispense it because it does have to be dispensed in a very specific way, held held completely vertically, right?
• 19:04
  SPEAKER_02: You shake it, hold it vertically, and then dispense.
• 19:06
  SPEAKER_02: But I always show my patients what the foam looks like, and I demonstrate how easily spreadable it is.
• 19:13
  SPEAKER_02: A little bit of foam actually goes a long way because of that ease of spreadability.
• 19:18
  SPEAKER_02: It has a very light feeling, and all that connects back to the excipient.
• 19:22
  SPEAKER_02: And I think I wanted to make one point.
• 19:25
  SPEAKER_02: You mentioned skin barrier.
• 19:27
  SPEAKER_02: Uh I just wanted to highlight that a study, transcriptomic study out of Mount Sinai, actually did show that there are certain skin barrier genes downregulated in seboraic dermatitis.
• 19:39
  SPEAKER_02: I do think you mentioned, Ted, something very important, which was the seboraic dermatitis, psoriasis, and I'll throw in atopic dermatitis.
• 19:48
  SPEAKER_02: Reflumolast works very well in all three of these, which is very unusual for a topical, uh topical medicine and formulation to work across all these uh immune-mediated inflammatory diseases.
• 20:00
  SPEAKER_02: But I think what we're seeing is actually decades of research into topicals, whether it's the active ingredient, whether it's the excipient, whether it's understanding the skin barrier.
• 20:12
  SPEAKER_02: I think what we see in Reflumoast, the foam and the cream, we see a beautiful coalition or coherence of all of these decades of research into creating a product that is not only effective, but it has all of those intangibles that we need to help our skin have optimal function, but also optimal feeling, sensation.
• 20:37
  SPEAKER_02: And you could throw in cosmetic and beauty because I think that that is the natural consequence of doing all the others.
• 20:43
  SPEAKER_02: And for the foam in particular, obviously patients don't want to put cream, ointments, lotions in their scalp.
• 20:52
  SPEAKER_02: And the reality is not just on the scalp, but otherwise elsewhere on the body.
• 20:58
  SPEAKER_02: Sometimes you got hairy men with hairy chest, hairy back, hairy whatever.
• 21:02
  SPEAKER_02: And having a foam formulation is fantastic for being able to go through these hair-bearing areas and get to the actual uh epidermis to get into the skin, uh, the medicine and to get the clinical effect that you want.
• 21:15
  SPEAKER_01: Yeah, and it's got that charge too, doesn't it, Chris?
• 21:18
  SPEAKER_01: I always talk about this with patients, that it's charged so that it's repelled from the hair shaft and stays on the scalp, uh, which is exactly where the pathology is.
• 21:26
  SPEAKER_01: And so there's just so much about these different formulations that makes sense for us to use clinically in our patients with these three inflammatory diseases.
• 21:34
  SPEAKER_01: And and Chris, one thing we haven't actually mentioned yet is the lack of some of the other irritants in the formulation, propylene glycol, for example, ethanol.
• 21:43
  SPEAKER_01: You know, there's certainly some irritants that can't that are often included in many formulations that we just don't see in Zurich.
• 21:50
  SPEAKER_02: Yeah, I'll add in polyethylene glycol, isopropyl alcohol.
• 21:54
  SPEAKER_02: And actually, there's no formalbehyde or formaldehyde releasing agents.
• 21:57
  SPEAKER_02: And it also, for those that there's no fragrance.
• 22:00
  SPEAKER_02: Right.
• 22:00
  SPEAKER_02: That's an important one for people that may be either irritated or allergic to fragrances.
• 22:05
  SPEAKER_02: It's also vegan and gluten-free for those that need that.
• 22:09
  SPEAKER_02: And it's, I think from that standpoint, it's a very well-designed vehicle.
• 22:14
  SPEAKER_02: I do wonder, are we going to see other topicals in the future take make use of such vehicle given the success that we've seen with reflumolast in terms of all of the factors we just discussed?
• 22:28
  SPEAKER_01: Yeah, I think that that Arcutis has really set the bar very high now for what we should expect from our topical formulations, especially for inflammatory skin disease where the barriers are already compromised.
• 22:39
  SPEAKER_01: And I completely agree.
• 22:40
  SPEAKER_01: I think other companies are going to have to meet, if not exceed, these this formulation standard in order to really be accepted by the dermatology community because we see what purposeful formulation with really unique ingredients, at least for the pharmaceutical products, does for our patients.
• 22:59
  SPEAKER_01: And then you also have to think about what's going on in skincare, Chris, where you've got companies making incredibly elegant formulations with very novel technologies that are also helping patients with inflammatory skin disease.
• 23:10
  SPEAKER_01: So luckily, the formulation science is pushing everything forward, both in pharma as well as as OTC skincare.
• 23:18
  SPEAKER_01: So everyone benefits from that.
• 23:20
  SPEAKER_01: And I just think we're in a great time right now.
• 23:23
  SPEAKER_02: Absolutely.
• 23:24
  SPEAKER_02: The innovation in topical formulation is off the charts.
• 23:28
  SPEAKER_02: And this is one example of a lot of successes coming together.
• 23:31
  SPEAKER_02: But you're right.
• 23:32
  SPEAKER_02: There's many other things that are being innovated, being able to use topicals to target specific cells in the dermis, such as fibroblasts, for example.
• 23:41
  SPEAKER_02: There's a lot of really exciting science.
• 23:44
  SPEAKER_02: I can envision many other things coming, you know, not just from an inflammatory or medical standpoint.
• 23:50
  SPEAKER_02: Obviously, there's concepts of anti-aging, longevity, all those types of products that are now entering our market.
• 23:57
  SPEAKER_02: But at the core of all of it, Ted, and I know you and I align on this, at the core of all of it is science.
• 24:03
  SPEAKER_02: If you don't understand the principles of the science behind the products, you can't really understand why a certain product may or may not be beneficial for a patient or succeed for a certain condition.
• 24:16
  SPEAKER_01: Yeah, and I think that's why this podcast episode is so important because we really dive into that.
• 24:21
  SPEAKER_01: Thank you, Chris, so much for sharing your unique expertise, uh, especially for these PDE4 inhibitors.
• 24:28
  SPEAKER_01: Your research and the publications have certainly helped me understand what's going on and how Reflumelast truly differs with its peers.
• 24:36
  SPEAKER_01: So um truly appreciate that.
• 24:39
  SPEAKER_01: Uh, everybody, thank you so much for listening.
• 24:41
  SPEAKER_01: My name is Dr.
• 24:42
  SPEAKER_01: Ted Lane.
• 24:42
  SPEAKER_01: I've I've had Dr.
• 24:43
  SPEAKER_01: Chris Bunick, an incredible expert in dermatology.
• 24:46
  SPEAKER_01: Again, his uh podcast is ABCDs in dermatology.
• 24:50
  SPEAKER_01: He has the wonderful Dr.
• 24:51
  SPEAKER_01: Lindsay Ackerman with him.
• 24:53
  SPEAKER_01: Uh, can't wait to hear more of those, Chris.
• 24:55
  SPEAKER_01: And you guys are doing a great job.
• 24:57
  SPEAKER_01: Uh, if you have uh any questions, if you'd like to send any questions over to us, you can send them via email inquiry at science of skinsummit.com.
• 25:06
  SPEAKER_01: We'd love to get your questions and make sure we answer those on a future episode.
• 25:10
  SPEAKER_01: Otherwise, of course, we've got the Science of Skin Summit coming up September 19th through the 21st in Austin, Texas.
• 25:15
  SPEAKER_01: And we just added a longevity meeting uh in February in Scottsdale.
• 25:19
  SPEAKER_01: So more updates on that is coming.
• 25:21
  SPEAKER_01: Thank you so much for listening, everybody.
• 25:23
  SPEAKER_01: Chris, again, thank you for your time and sharing your expertise.
• 25:26
  SPEAKER_01: We truly are benefiting from it.
• 25:28
  SPEAKER_01: Thank you, Ted.
• 25:34
  SPEAKER_00: Thank you to our sponsor, Arcutis Biotherapeutics, for their support of the Science of Skin Podcast and furthering Durham Education.
• 25:41
  SPEAKER_00: Arcutis is a medical dermatology company that champions meaningful innovation to address the urgent needs of individuals living with immune-mediated dermatological diseases and conditions.
• 25:52
  SPEAKER_00: With a commitment to solving the most persistent patient challenges in dermatology, Arcutis has a growing portfolio of advanced targeted topicals.
• 26:01
  SPEAKER_00: Arcutis's unique dermatology development platform, coupled with their dermatology expertise, allows them to develop differentiated therapies against biologically validated targets for a range of inflammatory dermatological conditions.
• 26:15
  SPEAKER_00: Arcutis strives to simplify disease management and optimize drug efficacy, safety, and tolerability.
• 26:22
  SPEAKER_00: They're determined to elevate the current standard of care, solving for the challenges others haven't.