Derms on Drugs takes on the AAD late breaking research, Part 1

Welcome to a special episode of season three of Terms on Drugs, a video podcast brought to you by scholars of medicine, the best educational platform in dermatology and provided in no cost medical providers. Terms on Drugs is we're cutting edge dirt meets, it missed comedy. I'm Dr. Matt Zeyer from Dr. Dr. Mertology and each week I'm drawing my marines and see buddies Dr. Laura Ferris from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh and we use our 60 years of combined derm experience to discuss debate and dissect the hottest topics in dermatology. It is everything you need to know to be a mechanical term and you'll actually have some fun listening. New episodes drop every Friday in Scholars and Medicine, Apple Podcasts, Spotify and other major podcast platforms and I highly recommend that you download the Scholars and Medicine app to access the full podcast video archive and explore the best derm educational content out there. Real, pharma independent coverage of everything that is exciting happening in the world of derm. There's a fantastic core curriculum. If you're new to this, if you're relatively new to derm, it is supported by an amazing AI clinical consultant called Ask Simon. So I mentioned that this is a special episode and the reason that makes it special. Me, Pat and Ferris sat in on the late breaking abstracts at the AAD and if you don't know, this is like where all the drug companies try and they competing to get in their best new data. They have like a whole gazillion submissions and they have a panel that picks like the most interesting cool list, hottest stuff and it's just all day on Saturday. So we sat in the dark room, watched us all day Saturday and we're going to tell you what we thought were the high points for the late breakers. So let's go ahead and get into it. Dr. Ferris, kick us off. All right, so I'm going to start with the abstract I'm going to start with was Reflume Alast and Kids. So this is the Integument Infant Study. So this is Reflume Alast 0.05% Cream, IE's or Reef Cream. An infant's 3 to 24 months with mild to moderate AAD. So this was an open label study and only lasted for four weeks. I had to have at least 3% BSA, mean age was 61 weeks, which I think is a little bit over one. That's impressive, Maris, that's good. Yes, it's math on the fly. Math on the fly. So although they only had to have 3% BSA, the mean BSA was actually 30%, but they're little, it's still not a lot of cream. So how did they do among those patients, about half achieved an IgA of clear, almost clear at four weeks, and 58% of infants reached an easy 75. And if you looked at two week data, that was 34%. So again, this was open label, so we don't have placebo numbers. Notably among those infants who had scalp involvement, like two thirds of them achieved a scalp IgA success, like zero or one. So they made the point that this was anatomically even better in the scalp. Kind of fits with what we see with Zory foam and scalp psoriasis. Agreed. They looked at things like, yeah, so maybe there's something magical about this drug in the scalp. I thought maybe it was the foam, but since babies don't have a lot of hair, you can do the cream on the scalp too. They did things that are cute for me, not as a pediatric dermatologist. They've got itch scores, or how does a 61 week old baby tell you how it's there? But apparently the parents give you that score and rapid itch improvement. Okay. How young did they study it down to? So they were down to as low as three months. So this was three to 24 months. I do, I have, seriously avoid taking care of young children. Is this, are there any other AD drugs approved to this young like, is Uchristzai? I mean, you're not going to consider Uchristzai a drug, but is it approved down to three months? Uchristzai is approved down, I don't know, I have to go look. It's approved down to a one age, I can't remember if it's down to three months. That's good for you. Because again, I almost studiously avoid, I think that the only thing I would use is like pro topic 0.03% or something is down to maybe six months. I don't know, don't take my word on that. Okay. But the babies did get interestingly, most common adverse event diarrhea and 3% or more. So, I know that's a thing, like kids, little kids poop so much, like you do it one day and you're like, oh my gosh, diarrhea is a side effect. The, the zoread is given them diarrhea. But it's not like we don't know. Yeah. Yeah. So, it's true. But I could see that happening in real life. If you're like, well, side effected diarrhea and after two applications of parents will be like, oh my gosh, yeah, this totally caused diarrhea. Right. But that's just what babies do. Yeah, let's see. And I'm looking it up right now. According to AI, our cutest plans to submit the NDA second quarter of this year, subbing standard Timon review. It's probably early 2027 that this will become FDA approved and prescribable would be my guess. Okay. Right. I mean, we need it. But not by any of us because we don't see anybody. I hate seeing kids don't see kids. We don't like kids. That's right. Yeah. Don't even care. Don't even care about kids stuff. Both of you have like a lot of kids, right? How patent how many do you have? I've like 13 kids. That's what your Catholic. That's right. We lost out. I have four boys. So you will be depending on somebody to take care of you when you're old because your boys will do nothing. Yeah. Right. My sons are not going to help me. Yeah. Ferret, Ferris. How many do you have three fairs? Three kids, two girls. I'm a good shape. Yep. You're good. You're good. Okay. I got I got two, but they're both girls. So I'm in good shape too. Okay. Yeah. Make fair. Can I borrow one of your daughters? That sounds weird. Never mind. Never mind. All right, Pat. And what do you got? The first one that I took was from the AM session molecular signals in skin aging. So tape strips were collected from the face and in our arm of 156 patients whose age range from 20 to 85. Actually, we should kind of say so that the entegument infant that was one presented by Lawrence I can fell. Who the hell did this? Who the hell can't happen? No, because they were tired. Molecular signals is healthy skin aging, highlight potential interventional anti-age targets using tape strips that was Helen. He. All right. So I'm glad you're doing this one because I paid no attention. Don't care. But most people care. That's some glad you're doing it. That's not nice. Yeah. They worked. They should get some. I hope Helen is not listening to this. Yeah. All right, Pat. 100 of 16 patients whose age range from 20 to 85 and RNA seek analysis was performed. The molecular signature of aging containing over 1200 genes was identified. Skin aging was associated with increased melanogenesis. I mean, that's not a surprise. NF cap of the pathway activation increased inflammation. Not a big surprise there increased oxidative damage decreased collagen. I mean, everything you would expect kind of interesting. They reported differences by race and so blacks and Asians increased cornified envelope genes. Black skin was the had the most significant down regulation in lipid synthesis, Asian skin genes that regulate reactive oxygen species in essence. Earlier immune activation peak white skin increased inflammation more than the others females had increased androgenization compared to males. Like a change, I want to say, like between sun protected and sun exposed. So the kind of what they were getting at is with this individualized skin care recommendations. That's where I wasn't sure. I mean, you know, reactive oxygen species inflammation. If you put on sunscreen, that'll probably help take care of that. Apply antioxidants. That's probably going to be across, you know, no matter what you're tape strip says. I don't see the recommendations really changing that much. So I don't know, I'm not sure what the, you know, ultimate application of this will be, but I mean, kind of a neat study. I thought does it get sort of differed by age? Like there was like this acceleration of changes in the in the 40 to 50 group relative to like the 20 to 30 group, right? Yeah, right. Like that was where the big changes seem to happen. Like in the 40 group and that's where you saw the biggest difference between that group and like, yeah, younger than 40. That's where you saw the biggest differences. So it was all in 250 people to tell me that. But yeah, yeah. I thought I remember earlier this year, there was maybe last year, there was some research in general for aging that there were like two state aging isn't like a smooth thing. It's like you age a lot in like your 40s in your 60s or something. Like not so much. And then you hit 40. And then you're kind of okay through your 50s and then like 65, whoo, you start aging fast again. I think I remember seeing that somewhere or I could be making it up either way. I could definitely see like some cosmetic East Durham spa person being like, we will individualize your skincare regimen. We're going to do this tape strip. It's going to cost you a thousand dollars. It probably costs like five dollars to do. And then they'll put together a regimen that it will cost an additional three thousand dollars. I can see it. You're right, I can't see it. That sounds like a good business model to me. Yeah. All right. Let's move on to mine. So I'm going to talk about, I actually don't even remember the name of it. It's the Amletelemab study, which is the Santa Fe's ox 40 ligands blockade, which was advertised heavily, heavily at the meeting. So basically, this is a fully human non depleting ox 40 ligand monoclonal antibody blocks ox 40 ligand, which fundamentally, this conceptually is totally different from any biologic that we have because it's not blocking a cytokine. It's blocking the coasting military signal between energy and presenting cells and memory T lymphocytes. And that is an upstream effect that can block lots of cytokines. And this both it and rookatinlamab, which is this one box to ox 40 ligand rookatinlamab by and so ox 40. So the basic takeaway here, the data is not impressive. So it's not at least at 16 weeks, not as good as do be. It may pick up steam later. The main potential benefit is that it may lead to a long term alteration and trajectory of disease. So if you do well on a mission or even even cure, although that's pie in the sky, but the problem is we're never going to know because none of us are going to prescribe it because it causes cancer. So this was a well known thing. So first there's cancer studies looking at stimulating this pathway, which is like, oh, say if you got cancer, we're going to stimulate this and it's going to cure you. But if we block it, no problem. So specifically the cancer that it causes is capizis sarcoma. And this was a well known thing. Like I was stunned whenever I found out the companies were developing this because it's a well known thing human herpes virus eight, which is what causes capizis sarcoma ox 40 pathway plays a very important role in suppressing it. So if you've got a hv eight human herpes virus eight and we blocked this pathway, probably it's going to activate and you're going to get capizis and son of a gun. It turns out that is the truth. So I do hope this comes to market because we do need additional options in somebody once they have failed. Dupy adbree, ebglyss, the rinvog, nmluvio and subinco, after they have failed all of those, then there would be a good role for this one that causes cancer. So that's that's where we will, we'll leave it. I would anticipate in each city, there will be literally one dermatologist who prescribes this drug and they'll have like four people on it, but they might also have lots of other indications. So that's the other beauty of this pathway. It should work in Vidaligo and alopecia, Arriata and psoriasis and like and planis and pretty much any inflammatory disease you could think of. So that there might be more to it than we would think, but main takeaway, probably not as good as Dupy causes capacities, sarcoba, but might give a long term cure. That's where because it specifically targets activated T cells, right? It's not. It's yeah, yes, it targets activated memory T cells. Yes. All right. Next, Ferris, what do you got? Okay. This next, this next presentation was on res, pagel, des luke and you know, I think of this as the, think of this as the brusque, rumpel stiltskin drug. Yes, we're going to call it res peg, which as did the presenter, David Rosemary, because nobody could say that name throughout an entire presentation. Anyway, what is this? It's an IL-2 receptor. So it's an antibody that targets the IL-2 receptor complex to stimulate regulatory T cells. So it's not like as opposed to your ox 40 ligand drug that is depleting or inactivating activated T cells. This actually stimulates the regulatory T cells, you know, the cells that won somebody the Nobel Prize in Medicine this year. Okay, by activating these, then you can actually bring the immune system back to balance. So that's sort of the mantra of this drug. As you may have guessed, because it has pag in it, it's pagulated. And so that gives it an extended half life. I could not get tested. First time I read even really. I would not have guessed it. Okay, resolve AA study. This is a randomized control trial. 92 patients got randomized to one of two doses of res peg or placebo. Primary outcome was 36 week, 36% reduction in salt score. So on average, these patients did have, you know, moderate to severe AA. So salt scores at baseline was around 80. So 80% of their hair was gone. And about a third of them had a salt score of 95 to 100. So these are like the people who basically have no hair. We know that these are the hardest people to get a response in. At week 36, the res peg group had a 30% reduction in their salt score, whereas the placebo group only had an 11%. And about 15% of the entire population that was treated went down to a salt score of 20 or less, whereas that only happened at 6.7% in the placebo group. 15%. So, so the average improvement in salt reduction in salt score in the res peg group was 30%. Okay, however, among the group who did respond 15% that had a salt score of 20 or less. Okay. So they had a good response. So no, this is no Jack inhibitor. Well, it's week 36, right? That's not like the jacks. The normal 30% is people to salt 20 at 24 weeks. Yeah, okay. That's what I had. Yeah, yeah, yeah. Okay, you're right. So it is not a Jack inhibitor, but, you know, I guess the question is like might this have a little bit better durability given that what you're targeting are the regulatory T cells, right? So could this have off drug effects? And so it's both the plus A and the minus, right, that it's not a Jack inhibitor. So like, look, dermatologists have shown, like we prescribe a Tesla that makes us the worst doctors in the world, right? We prescribe a drug that does not work is terribly tolerated, but we don't have to do any labs or talk about any side effects. So if you don't have to do any labs or talk about any side effects, we don't really care if it works is what we have shown as dermatologists. So this, well, yeah, I'm obviously trying to make, try to be a smart ass. Sure, yeah, we know. So speaking of side effects, they did point out that there were no, there was no evidence of increased mace, there were like no thrombotic events. There was not like a high rate of, you know, malignancy, jack signals, infections, things like that. They did notice some eocenephilia in the res pay group, nothing really stood out. Adverse event rate in the res pay group was a little bit higher, it was 97% versus 70% in the placebo. They did also notice some improvement in eyebrow and eyelash growth, but they didn't see any in the placebo group. So suggesting that there could be something there. So might it be effective but slower and the results did not, like they had not plateaued so they were still sort of going up at the end of the study. Didn't like 70% of people get injection site reactions? I think that there was a pretty high injection site reaction. That's because I, yeah, I looked at this somewhere else like a ton of people. I kind of wore that, I sort of blow that off, but yes. Okay. So don't weren't T regs studied like in the cancer world where if you gave mice a bunch of T regs and then gave them cancer, like their cancers were way worse because you had all these T cells basically shutting down the immune response. Like that would be my concern here. Like you are expanding. We're still worried about malignancy. Yeah. Yeah. So if you had a basal cell and you got res peg, I think the basal cell would go crazy. Oh my god. Well, so 0.001% would die instead of 0.001% so that make it melanoma or scramous cell. Okay, fine. That's all. Yeah. Injections like reaction rates were like, you know, like, you know, like, you know, like, fine, that's all. Yeah. Injections like reaction rates were like 91% of patients on res peg, but interesting 30% on placebo, which, who knows what we're looking at. Okay. I think he said like it doesn't, it's just Brett, like it's impressive to look at, but the patients don't complain of pain or itch. I think that's what he said. I don't know. Injections like reactions don't really get my hackles up that much. So if they just for our listeners, there's some interesting, there's some interesting and all the data that if you want to stimulate T regulatory cells, you also can just give people low dose method trexate. That's one of its primary mechanisms of action is stimulating T reg cells and low doses, higher doses. I think it does all kinds of stuff, but that's just interesting older data. All right, move on Pat and what you got. All right, my next one is the efficacy and safety of Dursamelagon and EPP. This is presented by Amy Young. So EPP patients have a defect in the final enzyme of hemsynthesis. Guys, remember that from residency? Faro-Kelatease. Yeah. Which key rates that iron into the hemolecule? It's also the enzyme that doesn't work as well in cancer cells. That's why PDT is more cancer cells specific because Proto-Prophora 9. Like builds up in cancer cells because they don't have that Faro-Kelatease enzyme doesn't work as well. What was the name of this drug again? Well, it was not for review ever. Yeah. What's the name of the drug again? Dursamelagon. That's what I'm saying. So wait, that's a character in the Lord of the Rings, right? It is. He was the head-- I have no idea. Sounds like one. It could be easily. Yeah. So X-linked proto-propharia is also due-- well, not also, but it's due to a gain in the function of one of the first steps in heme. So EPP and X-linked proto-propharia, they both have the issue of building build up of Proto-Propharia 9, which makes them very photosensitive. All right. So Dursamelagon is an oral MC1R agonist. It stimulates melanocytes to make you momellanin, which absorbs visible light. Study presented was a randomized placebo control face three trial patients. 12 and older, we're given oral Dursamelagon or placebo. Primary endpoint was the average daily sunlight exposure time to first pro-dromal symptom. And it was increased in the Dursi group on Connet Dursi. Secondary endpoints of global impression of change, number of sunlight induced pain events, non-pro-dromal photo-toxic reactions were all better in the Dursi group. Side effects, as one would expect, hyperpigmentation and moles, you get increased Nevi. So it's kind of a treatment that works similar to Afamelinatide, which is also FDA-approved to treat EPP and XLP. That's an implant that you get like every three months or something, and it's like a peptide analog of melanocytes stimulating hormone. So kind of the same effect that an MC1R agonist would have, although the Afamelinatide is less specific, just kind of care, I'm getting all these emails for EPP and XLP. This was one of the drugs why I think I'm getting that. There are some other ones by top per-bito-pertin and port 77. So we're getting these new drugs for EPP, which, I mean, I've only seen one case at like a grand rounds. I think we went onto West Virginia or something. Yeah. I was not kidding. I was not kidding West Virginia. I don't want emails for what you move. One in Pittsburgh too, also. OK, OK, we were residents. We were able to fluorescent diapers, right? We used to go down a pit. We were good out of here. Not in EPP. Remember that? EPP is not in the year. Oh, oh, yeah. OK, I remember. We were going to be one. EPP, no PPP. EPP, no PPP. Robin Garrett. So actually for the residents or anyone out, even attending's listening, if you think your patient has EPP, XLP, the screening test is free red blood cell protoporferant. That is the test you order. That's how you screen. And if that's positive, then you do the gene testing to see whether they have the pharochelites, pharochelites, deficiency, or they have that A. What did I say it was? ASA, ALAS2 gene deficiency. Really cool. So right. I mean, just meet science. Interesting aside was that the presenter, she's a pulmonary and critical care medicine attending, I think, at Mass Gen. She actually has EPP. So now we've seen two people with EPP. That's true. There we go. That was right. It was people. So these have got to be the dumbest companies, like imaginable. So they're studying this drug for the ridiculously rare disease when what they should be doing is asking Abvi to purchase the company and bring it to market as a combo treatment for Vidaligo. Right. So you get molotose to-- Or to be tan or full of Nevi. Yeah. Right? Like what if I always wanted? I wish I were moly or in tan or-- I would never-- If you could get a mole. And just once, if you'd like injected it intralesionally, if you want to-- Like the Maryland Monroe. Beauty mark right there, right? Oh, yeah. No, I don't want to make one of them. It is good to have people working on drugs that can help rare diseases. And I think it's kind of cool. But it's not like-- It's somewhat incompatible with any sort of normal life. Right? Yes. Yeah. So any help that these people-- That's the commercial market for this drug should be in Vidaligo. Vidaligo can buy it with a jack inhibitor. Speed it up. Speed it up. If you're-- It's an immunologic reaction against the melanocytes. I don't know that you can do it. But it's a lot-- I'm going to use it with Rinvoche. So Rinvoche to protect the melanocytes, and then this stuff to kick them in the ass and get them proliferating and migrating. OK. Because the big-- Yeah, Rinvo-- Vidaligo treatments take forever-- like you tell the patients, you'll be better, but it may take two and a half years. Right. Yep. Oh, sorry. Maybe you might want to make this. Hopefully they're listening. OK. All right, let's move on here. My next one was Kate. So my next one is actually what Patent's wife will be known as in 20 years when the AIs are running everything. KT621 is Patent's wife's nickname is KT for-- Is that far down on the list? 620. Well, there were 620 before her. KT621, KT621, first evidence demonstrating clinical activity and safety. So this is the breakthrough, in my opinion, for a topic dermatitis. So this is a stat 6D grader. So you take it, and it basically makes your stat 6 get metabolized and broken down. And so it is basically the equivalent of a jack inhibitor, but with the perfectly clean side effect profile so far. So as far as we know, like amazingly clean side effect profile, and to when I look at the efficacy, I think Jack efficacy-- so 30 milligrams of RINVO, 200 of ABRO-- but with a clean safety profile. So I cannot remember the name of the company, Kimerah. It's Kimerah. Kimerah. If I was a health care investor, I would-- which I do not ever invest in anything health care, because that would be insider trading. But if I was, I would be trying to get money into Kimerah, because this stuff is going to kill it. So just super effective drug, really interesting science. First, like the grader of a protein that I've ever seen. So just cool drug. And I have no conflict of interest with Kimerah. I'm trying to get one, but don't have one yet. So Kimerah, if you're listening, great drug. Good work. All right. All right, move on to our next one, Ferris, what do you got? In Voodessitinib and psoriasis presented by Andy Blow-Bout. So what is in Voodessitinib? It's a next-generation, allosteric, tick-to inhibitor. So you think about it as like next-generation, so tick-to. It provides, you know, each one of these has like a little claim to fame, maximal inhibition of tick-to over a 24-hour period. So studies were two parallel phase three studies, onward one and onward two. And they were head-to-head studies with both a primal-ast and placebo and Voodessitinib 40 milligrams twice a day. These were typical psoriasis base three, you know, Pazi 20, BSA 25%, BMI 30 kind of people. OK, what did the data look like? Pazi 100, that wasn't really their primary endpoint, but it's I think the most exciting primary endpoint. Pazi 100 scores were in Voodessitinib 29.4%. Well, not bad, not bad. Yeah, 29.4, 27.7. There's two parallel studies. A primal-ast, that was like 4% to 8% and placebo was less than 1%. Actually, maybe Pazi 100 was their primary. Don't ignore me. That's at week 16, at week 24, it gets a little bit better, like around 40, 41% for in Voodessitinib. And it still hadn't plateaued at that point. A primal-ast, it was 8.5% and 13%. So I thought that was pretty good. They did show scalp data, 75% of patients had a scalp IGA of clear or almost clear. About 48% in the a primal-ast group did. And they showed better itch reduction with in Voodessitinib, better DLQI, 0-1 scores. Safety, they had higher rates of nasopharyngeitis and acne. And interestingly, actually headache. So about 10% of patients on in Voodessitinib had headaches. And that was actually higher than what was even seen with the primal-ast. No death, no mace, no TB, no cytopenias, no significant lab abnormality. Right. So another point to inhibitor, but one that seems to work better, that's a pretty decent Pazi 100 response, right? So first two thoughts here, number one, like scalp, genital, all that stuff when people are like, difficult to treat sites. So far as near as I can tell every single drug that has ever been studied in a difficult to treat site works just as well in the difficult to treat site as it did in general services, meaning that they're not actually difficult to treat. Am I missing? Like difficult for patients to have, I guess. Oh, so maybe not difficult to treat. Maybe more just like high impact. Yeah, I think of them a little bit more as like high impact sites. Now that being said, a zero one of 48% with a primal last for the scalp. I mean, that's better than what we see for like zero one for a primal last on the body, right? Yep. So I do think that there's little differences. It's funny. I was just looking at this for another thing I was doing. And you know, there's things like palm, like if you look at the cheese, what am I blanking on the Ico tide at their special site data, like they did well on the scalp. They did well in the genitals, but like, palm, or what they call hand foot disease, which we assume is palm, or plantar, didn't really reach statistical significance. So I don't think that they're all created equally. Okay. Interesting. And it's a fair, it's just foreshadowing. I hope you're going to do the Zasso data. And when you do the Zasso, I want to hear your thoughts on which one of these is going to be a better drug, but we can wait till we get to the Zasso. You're going to have to wait. More wait. All right. Pat, Pat and what do you got? All right. This was another rare disease recessive dystrophic EB. So this was ABCB 5 plus cells and recessive dystrophic EB. This was presented by a can't read because this is so curable, demetra. All right. So already EB patients, they have biololic defects in the collagen, 7 gene, just like a horrible disease, right? We all know this is terrible. They show three pictures. And one was like a young kid. And it looked like he or she had no skin from the neck down, meant in deformities terrible. Therapies are limited. We actually covered one of the therapies in one of our prior episodes. So there's Vilsuviz, which is like a plant derived gel. There are two gene therapies, Vajuvik and Zevaskin. We covered Zevaskin. And that was where they took the patient cells and they transfected them so that they would make collagen. And then they made sheets of these transfected keratinocytes and put them in wounds. I mean, the results from that study was pretty impressive. So anyway, this is just maybe another therapy. So ABCB5 plus refers to a population of human skin derived mesenchymal stromal stem cells that express ATP binding cassette sub-family B member 5. That's what ABCB5 stands for. When these cells are administered IV, apparently they can have these anti-inflammatory effects. And I guess that's the point of these cells. It was a phase 3 placebo controlled trial. Patients either got 2 million of these cells on day 0, 17, 35 and at months 3 and 5. They're followed out to month 6. Patients receiving the stem cells had improvement in wounds and a decrease in inflammatory markers like IL-6 and stromal cell derived factor 1 alpha. So I mean, that's pretty much it. I could not figure out the science of this at all. I was like, why would you still not going to make any collagen 7? Yeah, right. I didn't quite understand it either. And it was like, okay, well, these cells are helpful for wounds. So they're not FDA, they're not approved anywhere to really treat anything outside of, I was reading that there's this center in Germany where you can put them into like chronic venous ulcers. And because I guess these chronic wounds have these high inflammatory markers, these cells, like given systemically tend to migrate to these chronic wound areas and they take these pro and inflammatory sort of environment and they call it down. So that eventually you would heal. But right, I mean, it's not like, it's not like the cells turn into keratinocytes that can make collagen 7. So I don't know. Yeah. They're all they're allo like they're from a non RDEB donor. All right, man, but still they're not going to make any collagen 17. I was confused. I thought it was something. Oh, these cells make collagen 7, but it didn't seem like that was the, it seemed like it, I, from what I can gather, it was this technology was felt to be something that can help heal chronic wounds. That's what they've been looking for. They've been looking for patients with chronic wounds and RDEB patients, certainly that. Okay. Okay. Yeah. All right. Moving on. My next one was zoom, a liko bar zoom zoom, a low kebar zoom, a low kebar. So for short, we're all going to call this one zoom and think about little tiny dogs running around the house like crazy after dinner when the little dogs get the zoomies. So zoom zoomie is a extended half life, I'll 13. So we're all going to be hearing a lot about this mechanism. So basically, apagee, and it has a sister company called Aruka, they take it basically existing antibodies. So I think this one is like basically, lebry that they make this white to amino acid thing that makes it bind to the neonatal FC receptor. And what that does when the antibody binds to the, I think the liver cells, normally it gets taken in and chewed up. And that's why antibodies have a half life when it binds to this receptor that goes into the cell and then it gets recycled and spit back out. And so this is an extended half life. You can basically think of this stuff as ebglyss with a 77 day half life. So it'll be likely a, maybe a Q3 to a Q6 month injection is probably going to be somewhere in there. The question is, you know, when you look at their data, my guess is it's not going to be any better in terms of efficacy than lebry or dupe. The data looks very similar to me. The main benefit is going to be you'll only have to get a shot, you know, two to four times a year. But the concern for me is, you know, we know dupe causes or througes that can be awful, nuance at psoriasis, it can reveal CTCL. And if you give a, we haven't seen much of that with lebry so far, but it might just be that it's too early. If we have the same side effects from blocking I/L13 as we get from blocking I/L4 and I/L13, then with this extended half life, it could mean that, oh, if you get the arthrauges or the psoriasis where the red face, we're going to stop the drug and it's going to take a year and a half for your side effect to resolve because of the extended half life. So it's going to be interesting to see what this drug is going to, like what their data is going to play out to be. If the extended half life fewer injections is worth the impossibly increased risk of side effects being long term or the conjunctivitis, for example, if you got the conjunctivitis, maybe it's going to be a year and a half. So it's an interesting thing. I think I'm not sure that this is the perfect thing for a deed drug for the ad drugs that we've got, but psoriasis, this stuff is going to be kick ass. That is very true. But so that's pretty much the extended half, basically extended half life, lebry, and I can't decide if I think this is going to be good or bad. But they're starting their phase three up late this year. So it's probably still three to four years out before it gets to market. Did they have data for things like psoriasis or arthoralges that do they see that or conjunctivitis or anything? But it's small and early. Yes. I think this was maybe the fact. Kimberly, for this was a phase one. I think it was a very small number of patients from what I remember, because this is the first data I've seen for it. So it was a small, let me see. I think I've got the numbers of patients here. It was a phase two, 123 adults. 123 adults. So, right, you would only expect to see two or three cases of nuanced psoriasis. So if you saw none, you wouldn't, like that's 50 chance you would see none, essentially. So, you know, we'll find out in the phase three. We'll find out in the phase three. We're doing the first starting up the phase two one here for it's basically like skyrizzy with the same modifications. So, you know, that would be potentially you can treat psoriasis once a year, once every six months. I just don't know how much, you know, I mean, I'm interested in it. I'm wondering if we'll have, you know, other, like impacts, I'll 23, we think is important for maintaining memory T cells. So maybe blocking it very, very consistently will help to have more of a remittive effect. I think it'll be interesting. But I don't know if patients, if you're like, here's a great drug. You have to inject it four times a year or you can have this twice a year. Like, do they care? Is that enough? I think the bigger thing with their I/O 23. is that they are giving it like triple the dose of skyreasy. So I am anticipating that literally a hundred percent of people will get a hundred percent better. Like if, 'cause it's, you know, there is data as they did what the knockout study. If you give people a massive dose of skyreasy, basically all of them get better. So like now we get what, 75% to pass a hundred or something or pass you 90, I don't know. But I think because they're gonna give such a massive dose, it might be better. That's the, yeah, might be better. All right, what do you got, Ferris? What's your next one? - Okay, my last one for this episode is you pat a sitnib in Vittaligo, video. Yeah. So two was two phase three studies of you pat a sitnib 15 milligrams for non-segmental Vittaligo 48-week end point primary outcomes were T-Vase 50. So it's like a 50, the Vase is like the Vittaligo Pase. T is total and F-Vase 75, which is facial Vase. So what percentage of patients had a 50% improvement in their total Vase score and a 75% improvement in their facial Vase score? 300, about 300 subjects per each study. So 600 total, little over 600. About 20% of patients on UPA achieved T-Vase 50 versus about 6% on placebo. And about a quarter achieved the F-Vase 75 versus 6% on placebo. Responses again, looked like they had not plateaued at 48. It did hit all its secondary outcomes like patient and physician, global impression, a change. Usual, Jack, side effects, acne, URI, no MACE, no VTE, because these are generally like younger, less obese patients. There were a couple cases as a zoster. I think this probably is not actually as good as what we see with topical ruxilitinib. And but I would also say in real life, I would use this with UV light with a little heliocare. You know, these are mono, maybe with even like a topical steroid, but these are monotherapy studies. So maybe there's room for improvement here. And it was the UPA 15 milligram dose. They did not look at going up to the higher dose to their. - What, did you, sorry, did you say what their facial, how many people got F, Vase 75? - Yeah. That was 25%. - Ooh, that is not a great number at 48 weeks? - Yes. - Eeks, eeks. Yeah, that's definitely not as good as Otesla, I think. Which would kind of make sense since high level. - Otesla? - Not Otesla with the hell as an absolute. - Otesla. - I think Otesla does better than that. I don't know if it does a ton better. I think it gets a third of people there at 48 weeks roughly. So, but yeah, interesting. Hmm, okay. Now I patent what you got. - Four. - That's a good question. What do I have? I think I moved in, I'm moving into the afternoon once. - Early memory loss, is that what you have? - About that for a while. It's late at this point. - That's a whole harmony. - By the way, I heard it right. It had a great joke this week in honor of Easter. - I'm going. - I'm going to have a whole line of rabbits. - Whole line of rabbits, a whole bunch of them, 30 of them and had them hop backwards. What is that called? - Hair line retreat. - No. - A receding hairline. - No, gosh. - That's so close. - Yeah, all right. Anyway. - I thought you were going to say one of the benefits of having Alzheimer's is you can hide your own Easter eggs. (laughing) - We're cutting that. Actually, no, we're not. It's patent year. - No, we're there. - I'm suffering from it. I think I'm allowed to make jokes about it. All right, so mine was Ordesicumab. This is an anti-Isle 15 medication. - This is exciting. - It was given, this was a study looking at Vidaliga. Yeah. - Yes. - Yep. Okay. - You're losing a lot of credibility here, Patent. - Yeah. - A lot of credibility. - I know that. - Because there's no study looking at, I can't remember what they were studying. The thing where you lose the pigment, it's the Vidaliga. This was presented by Brett King. So in the anti-Isle 15 medication is given sub-Q 300 milligrams every two weeks for six doses. Primary endpoint was F. Vasi 35 at week 24. There was no significant difference from placebo. So this was 40 patients that got the Ordesicumab, or Desicumab, however. And then 20 patients that just got placebo. So the primary endpoint, week 24, F, Vasi 35, no difference. Any patient who didn't reach the primary endpoint got narrow banned UVB until week 48. And so the Ordesicumab light arm did better than the control light arm. The numbers aren't listed in the abstract. And if they were in presentation, I didn't take any photos. So. - I. - Wait, you. So I guess you deplete CDAT cells. That's what the anti-Isle 15 medication does. Is it depletes the CDAT cells? And then you can give UVB and the CDAT cells won't be around to attack the melanocytes. I don't know. - Pat and bad. So the reason you didn't, for anybody who doesn't know Pat and the reason didn't take any pictures, he actually has a jitterbug phone. Doesn't even flip. It was pre-flip phone days. That would be a step up in his tech. - I have a Google. - I have a Google Pixel. Thank you very much. - Okay. - Just 'cause I'm not Apple. - You guys are such a. - I can't believe I get your screen text from you. It's awful. - Your phone snobs. - Yes, I found something. - I'm not giving in to the peer pressure. I'm my own man. - Okay, fair. Okay. All right, so that's disappointing. I was excited about the I/O 15 drug for Vidaligo, disappointing. Shoot, it was hoping for better. All right, last one for me. Villabella Mab, Vylobellumab, sounds like a beautiful antibody. Anything, anytime there's a bella, it's always basically beautiful. So Vylobellumab treatment for a very ugly disease, ulcerative pyodermic angrodosum, results of a multisentral randomized, we'll see if we can try phase three trial. And this is a cool drug. So it is an anti-C5A. So it blocks some part of your complement cascade and seems to have very little, even a impressive effect. So now you don't make neutrophil extracellular traps and that should help with pyodermic angrodosum. And it seemed to, so people had about 80% and 90% reduction in the volume of the ulcer, but placebo had about a 40% reduction in the volume of the ulcer. And that wasn't really placebo though, it was active control. So everybody got 20 milligrams a day of prednisone at the start of the study and then they had a required weaning. And it was just shocking how well the placebo group did to be quite honest. But it looks like the drug does something. It's just a matter of we don't know. It's like, PG's a hard disease to study. Like it's a hard disease to study. Think this drug does something, it'll be interesting to see if they develop it further. I think they're also studying it in HS where I've heard that it is very good preliminary efficacy. I'm gonna throw this out there to Abvy or to Aruka. One of you should be studying I-23 inhibition for pyodermic angrodosum. And then instead of us all, then when we complain, oh, you guys charge so much for these drugs there, whatever, but we did a study and people who have this horrible disease and they're so many like this many of them see, are we ethical? Yes, yes you are. But, you know, so I wanna see the I-23s get in on this disease, but if they don't, this drug will hopefully go further. - You wanna be that in on just for the sake of having an I-23 indication or do you have some mechanism of action that makes you think of it? - It's been preliminary, so there are reports, number of case reports, and I think even some case series of I-23 for PG and it works. I actually think it'd be a better thing for Aruka to study using the ultra-hydrocyle-23, 'cause I think that would probably work great. - One of the things that you can do though is say that I'm not really not sure if this is cutaneous crones [BLANK_AUDIO] or PG. Oh, there you go. Right, because TNFs work great for this stuff. Oh, yeah, but Sky Reese is approved for Crohn's too, huh? Crohn's. Yeah, yeah, yeah, yeah. I forgot about that. Okay. And there is a jab article within the last two years about like a delphy consensus of how do you diagnose cutaneous Crohn's? A skin biopsy is not one of the major criteria. So you could tell the insurance like according to this group of experts, I, the skin biopsy that I did, yeah, it doesn't show those granny loam is that is not one of the major criteria is that this delphy panel came up with. This could be cutaneous Crohn's. I just don't know. I'm not, I'm dumb. I'm not a good dermatologist. And that's very, anyone, any insurance person that's talked to me knows that that's totally believable. But I'm dumb. And it's, well, it's good. It'd be a good, you know, you talk about this group of experts said, if anybody ever quotes terms on drugs, they're going to be like in these three idiots said, sorry, we're the anti delphy consensus. The delphy not on that note panel. Or the dummy. What I want to thank everybody for joining this week. Join us this week for AAD late breaking abstracts and join us next week. We're going to cover another group of late breaking abstracts. So if you want to be on the cutting edge and know what's coming in the field with no baloney, join us again. So we hope you learned a few things. We hope you laughed once or twice. And mostly we're hoping you're planning to join us next week. And until then, I'm Matt Zyrus. I'm Tim Patton. And I'm Laura Ferris and we are terms on drugs.