Derms on Drugs takes on the AAD late breaking research, Part 2

Welcome to another special episode of Derms on Drugs. The video podcast brought to you by scholars of medicine the best in case of platform and dermatology and provided no cost to medical providers. Derms on Drugs is for cutting edge dermis, hit or miscommunity. I'm Dr. Matt Zeyer from Dr. Dermatology and each week I'm doing memory as in see buddies took to Laura Ferris from the University of North Carolina. Dr. Tim Patton from the University of Pittsburgh. We use our 60 years combined derming experience to discuss, debate and dissect the hottest topics in dermatology. It is everything you need to know during the cutting edge of derm and it likes to have some fun listening. New episodes drop every Friday on scholarship medicine, Apple podcasts, Spotify and other major podcast platforms and I highly recommend you download the scholarship medicine app to access the full podcast video archive and explore what is quite literally the best derm educational content out there. We're talking real actual education, not farma pushed crap, right? Coverage of all dermatology, core curriculum, what's hot, what's new, all kinds of good stuff and it's reported by an amazing AI clinical consultant called Ask Simon. So this week we've got as I said another special episode back into the AAD late breaking abstracts and let's get right to it before we get right to it. I do want to say the last week I finished on Bell Bill Bellomab for Pydermy Ganger-Nosom and then I did want to say that was presented by Dr. Ben Kaffenberger from the Ohio State University who years and years ago was one of my residents. I would like to say that I trained him, but mostly it was just that when he was a medical student, I was like, man, this guy's going to be the best doctor I've ever met in my entire life. And I was able to recruit him into derm and then stay out of his out way while he became a much better dermatologist than me. So now we're ready to get into it. Dr. Ferris, what do you got? All right. So my first presentation was exochysmab pluschers epitide for patients with psoriatic arthritis. This is together PSA of phase three B randomized trial. 15 minutes. Wait, wait, wait, why PSA? Why did they do this in psoriasis? They are doing it in psoriasis as well. Okay. Okay. But this is the first one. It actually was published like the day that the embargo lifted so you can actually find the whole paper. Okay. So what did they look at? They looked at efficacy and safety of exochysmab pluschers epitides. So talt plus a GLP one and compared to exochysmab alone and adults with active PSA who are also either overweight with at least one comorbidity or obese, meaning BMI over 30 primary outcome, which is a little funny. Like, yeah, of course, we're going to win this one was at week 36 the achievement of both ACR 50 and greater than 10% weight reduction. Okay. So like one group I star and then the other one I did not which one lost more weight. So okay. So 31.7% of participants achieved that outcome versus 0.8 achieved the, you know, with exochysmab alone. So you don't lose weight on exochysmab you do on terseptitide. Um, now, that is the best. You don't have to like to present the ratio of like, but are the treatment was 65 pounds more likely. Yeah. Eight thousand times more likely. Right. Okay. But I will say this that there was, they did just look at what percentage of patients achieved ACR 50 and for the combination it was 33.5% versus for exochysmab alone. It was 20%. So that is kind of a significant difference. It like twice as many got it on the combo. Yeah. So that's ACR 50. That's not just weight loss. So I thought that that would say, yeah, did they say was there a direct correlation between how much weight you lost and how much better your sorriotic arthritis got over the, uh, if they did, they did, I did not get that from it. Yeah. Okay. It may be like dug in the paper or somewhere. Okay. So, you know, and it kind of like, um, it achieved. So yeah, it was really like, they also looked at like what about ACR 20 plus 5% of weight reduction. And that was like 10% tall to alone 69.7% of the two drugs together. So yes, it does look like it impacts that now interestingly looking for, um, a little bit of psoriasis data in the paper. Um, so, you know, realize this is a PSA paper. So not everybody's got psoriasis and, but they did measure it and the people who did have cutaneous involvement. And they actually did show that the reduction in Pazie score was greater in the group that got both drugs. So a reduction of 4.3 versus 3.3 for the patients who got tult but not, um, to zip a tie. And again, these were not people starting with a Pazie of 12 or 20, you know, they may have had a Pazie score of like four or five. So, um, I think it's going to be really interesting when we see the dedicated study. Agree. This is, this could be a bombshell for Lily if it's like, if that, if the psoriasis data shows that it works twice as well with, I mean, you couldn't, right? It's already getting life. It was twice as well. People, 130% of people would get to, you know, Pazie 90. So that seems, seems unlikely. But if anybody can do it, it's Lily. It's right. Anybody can do it. It's Lily. Yeah. So interesting. I thought the ACR 50 alone being that different 20% versus 33.5. That was, I thought kind of provocative. Yes. All right. Here we go. Hold on. I had AI. Look it up. The short answer, the data suggests the PSA improvement is at least partially independent of weight loss. Marola noted that ACR 50 began to improve as early as week four before there was any meaningful weight change between the groups, which you flagged as a side that maybe there's impact beyond the weight loss. Okay. All right. Interesting. All right. Patent, what do you got? A Povor Sitenib in hydrodinitis of Pativa. Povor Sitenib is a Jack one inhibitor, probably more so than either Oopa or Aver or not probably. I mean, it is, right? Yeah. Abro is also super Jack one specific. They're probably probably this is even even more so. Abro has 10,000 times more Jack one than Jack two. This is 30 million. All right. Look. This abstract reported the data from two phase three HS trials, stop HS one and stop HS two. That's a great name for a trial. That's the best HS trial name ever. This was a big phase three HS study, moderate to severe HS. Povor 35 versus Povor 75 versus placebo for 12 weeks. They call it Povo. Povo is how the company refers to it. I don't care. I don't work for them. I call Povor. That's fine. And then they so they did 45 versus 75 milligrams versus 12 or I'm sorry versus placebo for 12 weeks. And then a 42 week extension of the 45 versus the 75. Both doses met the primary endpoint at week 12. They didn't give specific numbers in the abstract long term 54 week data is reported as pooled data between the two groups. So high score 50 58 to 66% of patients reached it high score 75 41 to 54% of patients reached it and like a high score 100, which I don't think any by a lot any HS treatment has given us high score 100 numbers 20 to 27% of Povo. People had that. Those are all pretty good. I think decreases in inflammatory lesions draining tunnel skin pain fatigue, DLQI. That was all reported statistically significantly better in the Povo group. There were three symbolic events one may event one death. They actually went over the death, not a terribly healthy person it sounded like. So yeah, I mean, I think Povo looks pretty good, right? I mean, those numbers are pretty good and it was phase three data. It's not like a phase two or whatever. Is that didn't we have did we have high score 100 responses for BIMIC Izzy map when we did the paper a few episodes ago. I think there's like a low rate, but it was in like long term extension and things like that. So, but yeah, so the interview with this is an oral medication that has the efficacy of BIMIC Izzy map. Yeah, I want to say it was like 10 to 15% for BIMI. Yeah. Yeah. So interesting. It is. It's going to be cool to have lots of at least multiple drugs that work for HS. It's going to be cool. Yeah, and I think what we're being interesting is seeing if you can like reduce the formation of tunnels and scarring and all that stuff. So, window of opportunity. Window of opportunity. It's all about the window, my friends. All about the window. That's right. Got to keep the window open. All right. Yes, with the window of opportunity, they were like, okay, if they have a high score of four, that's moderate to severe disease. So, you'll get you'll get them down to a one nodule and that'll be your 75% that'll be high score 75%. Right on. Yeah, that's right on. Right. Although they've been talking into a trial with that. just FYI. Right, they need five to get into a trial. All right, so my first one for this part blew me the heck away. So this was, and I forgot to take a picture of the title slide, but this was a laser for hair, endogenic alopecia, a padded alopecia, whatever the heck you want to call it, it was like a 1562 or a 1565 laser or something like that. And 1565 laser, I don't think it's commercially available in the market yet, but basically it is powered to like heat the hair follicle up enough to be stimulatory, but not enough to like kill anything. And son of a gun, the data was pretty impressive, and they showed before and after pictures, and it was pretty impressive. And this was monotherapy. So these people were not getting, you know, oraminoxidil, finasterides, brunalactone, topicals, PRP, like any of it. This was exciting. So this is one of the first things that I could imagine being a procedure for hair loss that is feasible for normal patients, right? Because I always think like, I mean, it depends on the pricing more than anything else, but I always say I just feel like PRP is too pricey, hair transplant are too pricey, like the majority of my patients are not going to do any of that. But you know, if it's 400 bucks to get this laser and you get six treatments in a year or something like that, I could see patients, and then you know, you'd want it to a year to maintain, I could see patients doing that. So this was pretty cool. This is new and new and important. So yeah, that's it. I'm still a fan of the red light therapy. The, you know, the red light helmets, they still sound ridiculous, but I do think they work. So yeah, that's it. You guys got anything interesting to say? No, I saw the pictures look good. I mean, it's interesting. It's interesting. I've been, I don't understand. I mean, I heard the explanation of like, it warms the hair follicle, like just enough, but it feels like that's not usually how lasers work, but it is. Pat, did you schedule your first appointment yet? I'm very happy with my receding hair line. Thank you. You could, you could probably get a discount if you're like, hey, I'm on this podcast. And if I come and give you if I show up with, you know, Fabio, like hair, that's right. I can give Fabio hair. I just choose to keep it short like this. What I wanted, like down on the forehead. So that fair. Like I just, I want this less of a forehead. Three quarters of your forehead, God. Okay. Yeah. They get a 3.2 head. I can't believe I've never heard that before. God. Anyway, moving on to the next. What do you got, Ferris? What's next? So this next one is Zazisitnib for psoriasis. So two randomized, healthy center, double blind, placebo, active comparative control, phase three studies, latitude, three, 001 and three, 002. So each, you know, these were pretty big studies, 693 and 1 and 11, 108 and two. So this was Zazisitnib, known as a next, another next generation tick two inhibitor, AI, optimized to have a very high affinity for tick two and high levels of inhibition compared to placebo and our old friend a primal last. Co-primary endpoints, PGA 01 or Pazzy 75 at week 16. So what did we see at week 16? About 70% of patients on Zazo reached a PGA 01 and in a primal last, that was around 30%. Similar, Pazzy 75, it was about, you know, low 70s percents for Zazo and it was 12% for placebo and a primal last around 37 and 33%. They did at Pazzy 100 numbers and those were 33% and 25% in the Zazisitnib group. I reached a Pazzy 100 versus placebo, it was 0.7 and 1.1 and in a primal last, it was 2.9 and 4.3% at week 16. AEs that they saw were URIs, nasopharyngeitis, kind of a high amount and then acne as well. If we look at, they had some week 24 data, Pazzy 100 was like 42% and for Zazo sitnib 32% for primal last and right, no, am I reading that right. Pazzy 100 at week 24 was, yeah, Zazo sitnib 42% of primal last 5%. So now you're going to ask me which one's better in voodoo sitnib? I don't know, I still don't know, I don't have the answer. I mean, it's still like not huge study side, it's not huge. I mean, the Zazo study is definitely a bigger study and I don't know yet what I think. I mean, the numbers versus the primal last, I mean, they're kind of similar, right? There's not enough for me to say it's 100% this. Do you have a feeling? Well, they, no, I do not. I like Takeda, they're kind of, they're a cool company, the super old company from Japan. More my thing that I wanted to discuss, I, so this is going to be a controversial take unlike most of what my takes are. So I think that I could hide is going to be a disappointment. I think that the take on an empty stomach is going to make it, and the pharmacokinetics of it, I think you're going to make it so that if people are not 100% compliant, like perfectly, that I think we're going to not see the phase three results replicate, or I'm sorry, the clear life, you replicate phase three results. Now this is a steep Feldman question. Yeah, the withdrawal rate, like if you look at the loss of response when you stop IcoTide, it's not like it drops off like this. It could be gradual. So there is still some IL-23 effect, one, two, not taking in on an empty stomach. It will decrease absorption a little bit if you take it with caloric food, so you could take it with a little black coffee and you'd be fine. And it's 30 minutes, right? So is that the end of the world? I mean, do you really get up and like stuff? I definitely get up enough coffee within 30 minutes, but I don't know that I get up and have like a meal within 30 minutes. So maybe you reduce absorption by 20%, it's not like you blow up or something. Like you don't explode if you have food. So it's not like, you know what I mean? I don't know. That was, did that was that an adverse event of special interest? It was. Yeah. So there should no explosions. So here's what I would say. What do we always say? A Primalast is, Oh, Tesla does so well because you don't have to check any labs, right? I could try it is now approved. You don't have to check any labs. So if you have a better drug where you don't have to check any labs, I still think it's going to be people use a ton of Primalast for not checking labs and it does not work very well. That people want to, if I was in a clinical trial for Otezla, I would be hoping to get placebo. So that didn't have to worry about the nausea and the diarrhea. You can basically equal odds of getting nausea and diarrhea as you do of having it work. It's just crazy, crazy. All right. Move it along, Pat. And what do you got? Sonalica Mab. So sonalica Mab is a nanobody. It's like, it's like Bimzelix. It's anti-IL-17A and F, but it's like it's like Lucy Goosey. Like Bimzelix is rigid and stiff and it can't like make tight corners. And Sonalica Mab is smaller and it's like flexible. So it's like you and me. You're kind of like the Bimzelix is a patent in the Sonalica Mab is a virus. I don't know. I think I'm pretty Lucy Goosey, but fine. Is it not smaller? Is it not smaller also? It's smaller. So it is like you. It is smaller. Yes, it is. So not smaller. I want to say the flexibility. I don't know. I just like the idea of like this wavy flexible, but you're right. It's also smaller. So the linking thing is something that binds to albumin and that's a big part of it. So with a small molecule, what you'd worry about is it will get filtered out of the kidneys pretty quickly. But by binding it, but because it kind of piggybacks along albumin because of that center portion of the nanobody, it doesn't get filtered out by the kidneys and albumin tends to also get to sites of inflammation. That's just a thing albumin does, I guess. - But doesn't the albumin keep it from getting out of the blood vessels? Doesn't it need to get out of the blood vessels and into the tissue? - Not apparently, like not when there's inflammation, which is why you think of serum and plasma like that kind of reaches out when you, yeah. So kind of neat technology. - Okay, is it, can you, didn't you say this comes from a weird thing like a? - A camel. - A camel. - I was thinking, for some reason, and it was an octopus. Okay, it's a camel. - I don't think that's how I make antibodies. I'm just gonna go on record of saying that. I could be wrong. But, how can you, you couldn't live without antibodies? All right. - Yeah, so I'll make my antibodies. - So Sonalic Amab in HSN, dosed every two weeks up to week six, and then every four weeks, and then the placebo group crossed over at week 16. This is data from week 40. This was the Vella one and Vella two trials. So I mean, so just, you know, going through the numbers, high score 50, reached by 75%, high score 75, reached by 60%, high score 90, by 35%, high score 100 by 25%. So on the higher end, high score 100, that's pretty comparable to what they saw with the POVO study. But the high score 50 numbers, the high score 75 numbers, I mean, little bit better than what the POVO data showed. So just to go back, the high score 50 on the POVO was 58 to 66, and for Sonalic Amab 75. - Whoa. - And I'm sorry, go ahead. - Oh, this is the hospital. - Whoa. - Whoa. - Yeah, no. And I mean, technically was a little bit shorter too, but it was 40 weeks in the Sonalic Amab, and they looked at it at 54 in the POVO. But just like really impressive numbers. And again, these are phase three trials. This isn't their early stuff. And yes, so I think Sonalic Amab, that one looks pretty excited. Rates of oral candidysis weren't reporting the abstract, but AI looked it up for me. And if I believe AI, which I do because I'm too lazy to verify anything and tell me, 7.3% saw oral candidysis compared to zero point four in the placebo. - But that's better than BIMA's, than BIMA Kizumab. - BIMA's a little bit higher. I thought that was pretty interesting. And I remember when we looked at, we reviewed a network meta analysis and sonalochimab was also in there. And they basically said like, it looks like it's the most effective one, but it's not really powered. Like that P-value wasn't significant like as it was smaller studies. Now that we got phase three data, if somebody reruns the NMA, it'd be interesting to see if it comes out. - Yeah, I remember sonalochimab being at the top of that NMA. And I had not even heard of sonalochimab at that point when we reviewed that earlier. - I think I'm gonna call it sonalochimab, just to stake our claims on pronunciation of everything. - Sonalochimab. - Yeah, that's what it looks like. - Sonalochimab. - To me, it's not as no longer a nano body, it's a camo body. - It's a camo body. All right. They're pulling up a higher risk for marketing for this job. Okay. - This is early draft stuff. This is great. - This is way more stuff. - We'll refine there. And they will be coming to us asking, what's the best plan? - So, I'm very next to what. I don't think I told you guys I was gonna do this one 'cause I forgot it was out there. DuPillamab reduces key Lloyd dimensions in Holtz Fibrosis. So first, I'll tell you the part that I think is exciting. So weekly Dupy versus placebo for 24 weeks followed by crossover. And so people got up to 52 weeks of Dupy. And it was statistically significantly better than placebo from week eight on. But the total percent reduction in the height of the key Lloyds, 12.9 percent. So not like, ooh, it makes your key Lloyds melt away. And so I don't think this is going to become a monotherapy for key Lloyds. But what I could see is you go on Dupy, get your key Lloyds excised, injected, we like whatever else we would do to a key Lloyd. And we might see that combo therapy makes a lot of sense. Like this is the other drug, just if no people haven't seen this before, there's some data out there for pentoxophylline as sort of combo therapy to help prevent recurrence which is cheap and easy. AI and you'll find everything you need to know about it. But that's interesting, cheap and easy one. But Dupy, people I'm talking about, Dupy for key Lloyds for a long time. And this was the first to me quality data that says, yes, it definitely does something, doesn't do enough on its own, but it definitely does something that might be good as combo therapy. That was kind of my takeaway of it, right? - Okay. - And it is, they gave it systemically, they didn't do it intrelationally, right? - Correct. They gave it systemically, yes, that is my, I'm 99% certain of that. - Oh, yeah, it was. - Yeah. - I mean, it's way impractical. I mean, the pictures were impressive as monotherapy. It's like, yeah, it seems to treat key Lloyds. I couldn't imagine the key Lloyds spontaneously getting the response in the pictures that they showed. - It really really seemed practical though. What's impractable about a weekly injection? Once a week. - It's $400,000 a year. - Oh, what would it be? It'd be $120,000 a year to get a response that you could get with intrelational tack. Like, when I saw the pictures, I'm like, I'll tack would do the same thing. - Okay, fair. - I'd never thought of key Lloyds as a TH-2. - Like thing. - So that was interesting. - I don't think it is a TH-2 thing. I think fiberglass have the I/O13 receptor on them. I think I/O13 directly activates key Lloyds. Yeah, activates fiberglass. So it's not, now maybe that's part of the TH-2-ness or whatever, but I don't think it's a general and slamatory thing. I think it's just that I/O13 receptor is literally on fiberglass. - Cool. - All right, move along, fairs, where you got. - All right, I'm gonna double up, which means you can skip me on the next round. So these were two abstracts basically by the same company looking at the performance of something called Derm Plus. What is that? It's an iPhone program. Basically it's an iPhone with a dermatoscope on it and you get the adramascopic image and it classifies lesions as benign or malignant. There is this device called Derm, which is used in the UK and they state that this is actually, it has more advanced, that one has more advanced AI than Derm Plus. So this was it, these were like US and Italy based studies. So the first study was like how precise is it, meaning how repeatable and reproducible is this for AI detection? So what they did was they used Derm Plus to assess lesions that were already scheduled for biopsy. So everything got biopsy. It's a prospective cross sectional multi-center study. This one was actually done in the UK. Sorry, the next one was done in the US and Italy. So each lesion was basically multiplied, was imaged multiple times by three different operators using three different smartphones. And the images were assessed by Derm Plus. And their aim was to show, and so there's a little bit of like how accurate is this too, not just how reproducible is it. So the endpoint that they were trying to reach was to demonstrate the average positive agreement for repeatability and reproducibility of greater than 80% for malignant lesions, and the average negative agreement for greater than 50% for benign lesions. So 115 patients were created. They had 61 malignant lesions. And those were mostly basals and squames, but there were 11 melanoma. There's only one sub-K here. I thought that was interesting. So the APA was 100%. So it detected all the cancers, and it was repeatable and reproducible. And then the negative, the average negative, the ANA, was 80.8%, which was-- and no, sorry, the repeatability ANA was 80%, the reproducible ANA was 64%. So it didn't-- it wasn't quite as much agreement there. But it was achieved a sensitivity to malignant lesions of 100%. The specificity was 18%. So-- Wait, wait, wait, wait, wait. Do you want me to re-explain APA and ANA? Yes. But I also just want to make sure I understand the specificity. So that means it was. wrong. It called things malignant, things that were benign. It called the malignant 80% of the time. Yes. This is the problem with most of the devices out there. So we'll pick up the malignant things. The problem is it doesn't, so it's high sensitivity. It does not allow specificity. Okay. And what's APA and A with absolute positive? A average positive agreement and average negative agreement. Like how much do we all agree? Yes. This is a cancer or how much do we all agree? No, this is not a cancer. Okay. Yeah. Okay. Okay. Okay. Okay. Okay. So that was like re, so, so sensitivity, 100% specificity, 18%. Second study, clinical validation study. This is done in 16 dermatology clinics across the US and Italy. And so they're sort of threshold and there's a word for this that's escaping me. But looking for, they wanted to see a sensitivity for melanoma of greater than 90% and a specificity for all malignancy of greater than 20%. This was over 1,000, over 1,100 patients, over 1200 lesions, 513 of those were cancer, 126 were melanomas. Sub-K number here was interestingly 77. Okay. So they looked at sensitivity. How often did it accurately? If something was a cancer, did it call it cancer? For melanoma, it was 93.7%. And for squamous cell, it was 100% for basal cells, 99%. And the specificity here for non malignant lesions was 24.4%. So they did use a panel for a dermatopethologist for the pigmented lesions. So you know, derma, derma, derma, derma, derma path A's melanoma is not always derm path B's melanoma, little more agreement for things like basal cell. And so, you know, their goal is to try to market this in the US for, you know, evaluating pigmented lesions. The way they use this in the UK is in, you know, in this slightly different version is you go to a GP, you've got a skin lesion, they put it through. If it says nope, that's benign, they do not refer you to dermatology. If it's positive, then you get referred to dermatology. So I don't know, I don't know what their goal is, if it's like they, they want dermatologists in the US to use this. There's a little bit less regulatory hurdle. If you have a tool that's a decision support tool for a dermatologist, you know, then if it's like a standalone diagnostic device. So if I'm a dermatologist, I'm getting this immediately. 80% of the time it tells you to biopsy. Well, you know, we can make a good study in the US dermatologist select lesions. The specificity was higher as 24.4%. So it didn't. 24% in that case. Well, fine. I'm gonna tell you to biopsy 75% of the time. So you use this. When I was with the original studies on melifying, this specificity was 10%. So it told you to biopsy 90% of the time. Well, I remember we were in that hotel room drinking, not just the three of us. It was a whole group of people and we told that we had a melanoma. Yeah. I don't think I told them me had melanoma. I think the device said suspicious lesion. But did you get it removed? Did you get it removed? Yeah. Man. Yes. What's I know. It was benign by the way. Matt didn't even care what it was. Yeah. Just. It was benign. You're gonna be a what's no matter what. But yeah. So yeah. This is going to be the challenge. Thanks for your. Thanks for your concern. So you're trying to tell me your hair loss is from chemo. That's what I was. It would have made sense. Yeah. I mean, so the problem is going to be how do you use this? If you're like, let me put this on everything that the patient is worried about, you're going to do a ton more biopsies. If you say everything I'm planning to biopsy, I'll use this on. Maybe it will reduce your biopsies by 25%. Hmm. Hmm. No, we got to use it on everything. We don't think we're going to biopsy. If that's true, if your goal is to do a lot of biopsies, that is the intended use then yes. That's probably the best way to do it. All right. So now what about the Ameri. Wait, did you already cover the American study? Yeah. That was that the second one was UK. I'm sorry was US Italy. The one that had the 1100 plus patients in it. So how close first? I know you're like world expert on all of this. What's the one that's coming that is like the full body polarized or microscopy? Is that making its way towards utilization? I think it's not commercially available yet. So basically the robot that can go around look at all the moles and do such high, high, you know, resolution close-up imaging that you get what looks like dermoscopy. I think that will be interesting. I don't know where it is in terms of being available. I know that it is being worked on to be a commercial product. I mean, to me, then you can have AI that can, you know, pick out the most atypical lesion. It can. You can do. To me, these are going to be helpful as serial images, right? It's not just what it looks like now. If it's not changing, it's not a bad cancer. We could leave it. So if we only look for things that change, we might be able to actually find biologically relevant tumors. That's my hope for our future. Yeah, change. That's change right on. Change. Yeah. Yep. All right. Patent, we got next. LP003 for CSU. This was presented by. Dr. Gough. You don't want to present it. Just tell us what happened. I know, but they got up there and spoke and I think they want to be acknowledged. I'm still going. Unless they happen to be matched resident, then it's important. Yeah, right. I mean, you really singled out your resident. We were supposed to be an unbiased dermatologist, like, someone that listeners can trust and you're blowing it. Blowing it. Blowing it. LP003 is an anti-IG antibody with enhanced affinity, enhanced FC-Upsilon R1 inhibition, and longer half-life compared to OMA. So this was data from a phase two trial, three doses of LP003, compared to placebo, and the 300 monthly dose of OMA. So there's lots of numbers. I like. I always like the proportion of patients reaching UAS7 at zero, right? That's what you. You want the patient to come back and be like, "I don't have a hives anymore." So those numbers, 44.4% for the 100 milligram every eight weeks of this new drug, 66.7, for the 200 milligrams every eight weeks, 57.5 for the 200 milligrams every four weeks. That was a little bit odd that the 200 milligram every four did not do as well as the 200 milligram every eight, a little bit odd. How did OMA compare 43.6? So it was better than OMA. If I see that it was 10% better. Yeah, that's pretty good. That's pretty big, right? Yeah. So similar sorts of numbers for the least squares mean change from baseline blah, blah, blah. Week four data seemed to indicate that this superior response happened pretty quickly. So there's a new shiny anti-IG antibody. Kind of interesting. This is like Dejavu, right? There was a phase two trial, like a LISMAB, bound to higher affinity anti-IG, phase two data. It looked really, really good. And when they came out with the phase three larger study, it was really no better than OMA LISMAB. Whoever made like a LISMAB, I forget who it was, they stopped pursuing that indication based on the phase three data. So we'll see what happens, but preliminary stuff looked pretty good. Okay, fair. That's good stuff. Okay, so let's see my next one. Evacucine safety of Adversity nib in patients with chronic hand XM, right? Noise of a blind multi-center, Pacific soil trial. And I will give you the takeaway. It works really, really, really, really, really, really, really, really good. For a while. Yeah. 80% of people do, like 80% of people do phenomenally well. So basically, I would say it's just as good in hand XM as it is in a topic dermatitis. And that's interesting because hand XM is primarily irritant dermatitis. And then there's some contact germ in there, and there's some a topic germ in there. But so this is interesting because the way that we should think about hand XM, you need broad spectrum anti-inflammatory that does not impair the skin barrier. Because that's the problem with steroids is you take steroids for three days. You do a topical steroid for three days. Your skin barrier is dramatically impaired. And so it helps bring down the non-specific inflammation from the irritation. But then it's making the barrier worse. You use a jack inhibitor topically or orally. And you can bring down the inflammation without destroying your barrier. And so it's interesting what you would have predicted. But still interesting. So that's where we are. And so I think the numbers are certainly better than for a topical jack. which was interesting. I would have predicted that oral topical jacks would have worked better, but it does look like my guess is the oral is more effective. So, it's where we are. - My summary, yeah. My summary of this is chronic hand eczema is a topic term. Abro works for a topic term. Abro works for CHE. So that's Pat, you're giving a logic class now. - Yeah. - Okay, let's see. The CHE thing is driving me crazy. I'm like, this is a topic term. - No, it is not. - It is. - Let me show you. - Here, you know what? I'll go full zyros and don't ever, my advice to anybody, never go full zyros. - Yeah, I'll go full zyros. - Yeah. - If my full zyros is, if you diagnose your patient with chronic hand eczema, you are a dumb and bad dermatologist. Because you have taken a whole host of medications that work really, really well for things that are a topic term and taking them out of the picture and allowed your patient to get one FDA-approved therapy. You diagnosed that patient with atopic dermatitis, hand predominant atopic term. You have 12 medications and when amletil meb gets approved, 13 medications that you can give your patients that'll make their hand eczema better. Patent, that's actually reasonable. See, that's, you went full zyros, that's the most sense you've made to me. - I don't feel good about that at all. - I want to go take a hot shower. - You mean you would go to the cold shower. - That's what you really mean. (laughing) - What you're actually patent. - I do not. - Oh, we're skipping spares. - I've been there. - I've been there. - Okay, fine. Let's go, Brepocytinib. Brepocytinib is an oral tick-to-slash, Jack one inhibitor. It's like a molecule that binds to both. It's kind of neat. It's like a horseshoe. - This is insanity. This is nuts. - Abstract presented data from the valotrol, which actually was published, I think, the same day that Dr. Vloegles was presenting this data. This is a study of 211. - Did Vloegles or Vloegles actually don't know? - Vloegles. - She won't talk to me personally, so I never get to ask her what her name is. So this was 241 Dermatomized Sitis Patients underwent randomization. 30 milligrams, Brepocytinib, 15 milligrams, Brepocytinib and placebo. Primary endpoint was something called the mean total improvement score or TIS. Higher scores meant greater improvement. So 30 milligrams, Brepocrypt statistically, is typically better than placebo. 46.5 TIS to 31.2. The 15 milligram group was numerically, but not statistically significantly better than placebo. There were nine other secondary endpoints. I'm not gonna go through all those. The Brepocytinib, 30 milligram group was superior in all of those nine endpoints. There were two skin-related charts. So I actually went through the new England Journal Medis. This wasn't covered specifically in the little abstract, or maybe it was, but the two skin-related charts in the New England Journal Medicine article, the Lee Squares mean change in C-dassy, which we had a rheumatologist on and Matt called it the cadassie. (laughing) She laughed really hard at that one, I think. (laughing) So the change, the Lee Squares mean change in C-dassy was minus 11.7 for Brepoc versus minus seven for placebo. In patients with moderate to severe severe disease in patients. What are those numbers mean? I have no sense. I know what like easy 75 means, I know what passing, I mean. What the hell is that? I think what she said when she was on is, like a difference of three or four, which that wouldn't seem like that much of a different, like that's clinically meaningful. Okay. I think I remember her kind of saying that. Yeah. In patients. Yeah, go ahead. Okay. In patients with moderate to severe skin disease at baseline, so these were patients that had a C-dassy A of greater than 14. 44% reached cutaneous clinical remission at week 52 compared to 21% of placebo patients. So big difference. Side effects, serious infections, that one kind of stood out. Serious infections occurred in 10% of the Brepoc 30 milligram group compared to 1% of the placebo. They made a note in at least the New England Journal article that they didn't have to stop therapy to have to be treated through that, but it was classified as serious infections in those patients. So Brepocytinib, I mean, for a tough disease, a bad skin disease, these were patients with both skin and muscle. So it wasn't just, they didn't have like a clinically amyopathic, amyocytis group in this study. But pretty, pretty impressive numbers. I'm kind of excited about this one. Yeah, the pictures looked really amazing since we're simple dermatologists, pictures are good, but yeah, they looked really good. This is exciting. This is such a tough disease. Yeah, great. This is like if there's a disease. These were not. Yeah, these were not patients naive to other therapies, right? I mean, a lot of them were still on-printed. So it wasn't like a true placebo group. It was patients that were on other therapies that had failed like IVIG or Tuxamab. Like if they were naive to any other therapy, that excluded them from the trial. So these were patients who had been on therapy or currently on therapy through the study, but they just weren't responding to the therapy. So these were the patients that we see. They're on the Plaquenil and the Ritux and the IVIG and they're not getting any better. So this is pretty nice. Yeah, agree. All right, last one. Rad dimicabart. This is a next generation I/O4 receptor alpha inhibitor. So binds to a different part of the I/O4 receptor alpha than dupe has a higher affinity for it than dupe and they have finished their phase three studies. They're for a AD. Their asthma studies are ongoing. Their COPD study. Space two is ongoing, but actually, so this is a drug that I've not been following terribly closely 'cause I'm like, "How much better could it be?" And so it's probably better than dupe. The 52 week numbers, 96.6%, easy 75, 87.1%, IGZ zero or one, 85.3%, easy 90. Now, the 52 week data though, is we don't have any comparator arm and I'm not certain if those are as observed numbers or if they are modified or NRI numbers. Because when you see a number like 96.6%, that usually means to me that there's something weird with the study. Like nothing, you just don't see numbers like that. So-- - That wasn't a statement sub-response. That was actual response. It wasn't like, "Oh, if you had a PAS or EZ 90 at week 16 and you continued." - Yes, I-- - There was through response. - I think like it's the abstract and I wanna see like the whole paper and the whole thing. That would make way more sense if it was maintenance of response. It's hard to believe, 'cause whenever you look at dupe, and you say, "Okay, what if we give dupe every week instead of every two weeks, it is statistically no better." And that shouldn't, if it was just that you're binding more, if you double the dose, like you should see a big thing, maybe it is the fact that it's a different epitope. But yeah, I'm excited now to see the full article come out. To really dig into this and see if I can figure out why they are somehow tricking me for how good this drug is. - I like how they're probably tricking you. That's-- - That's probably what it is. - I mean, I'm easy to trick. - True. - I'm easy to trick. I'm very-- - So much. - If I wanna believe it, I'll find a way to believe it. That's it. I don't wanna believe, but I'm so far, I'm believing it. Let me see, I've got AI running in the background. Let's see if it will tell me if that was a maintenance of response or a total response. Let's see here, come on, my computer's not running slow. There it is, that's what I need. Let's see, based on the available reporting total response at week 52 not maintenance among 60. in response, Zao, the presenter framed it. Responses continue to improve over time with IG 0 and 1 in the easy 75 rising to 87.1 and 96.6, respectively by 52 and that language rising to implies a cumulative rate. - It does, okay. - We'll see, right? - We'll see. - Do you have AI record the sessions? - It was how he was quoted in, you know, - Some other, yeah. - And on, - And dermatology, - Pyrrhebide, - Pyrrhebide, - or some phylinic, as well. - Yes, sorry, got it. - Okay. - Yes, one of those spammy emails. All right, go with Ferris, what do you got? - Okay, I have interleasional PD1 intratumal therapy. So this is a dose escalation study. So this is Intacilph762. So what is this? You're like, oh, another interleasional PD1. It's actually a small inhibitory RNA that you goes into the tumor cell in silences PD1 mRNA inside the T cell so that it doesn't prove, it doesn't express PD1. So interesting, the different than an antibody bonding to the surface. And it is, you know, in like a cholesterol backbone so that it gets endocytosed inside the cell. So phase one B, dose escalate, they just basically did like dose escalation study. And they looked at three different cohorts and they could have squamous cell carcinoma, which was the majority of the patients. Melanoma or merkle cell and they got weekly doses for four weeks and then they had their tumor excised. And then they could look at things like pathologic response as well as clinical response. So 22 patients received the drug at different doses. There was, they did not reach like, "Oh, this is our dose limiting, there's no dose limiting toxicity "so they could have gone higher." 20 of these patients had squamous cell carcinoma. 10 of them actually had a complete pathologic response so no viable tumor, four had a path partial response. There was a patient, one patient with merkle cell who had a partial response and one patient with metastatic melanoma who had no response. If you look at the higher dose cohorts, they did look like they numerically did better. So when they used injectable recessed response criteria, they only saw 15% complete response but this is kind of what happens with, sometimes with more neo-aggiband treatment or interleasional treatment is that you get this robust immune response. So the tumor looks bigger and more inflamed but it's really the immune cells that are in there not the tumor. But this was, I thought, really interesting. So basically 50% of the ketaneous squamous patients had a pathologic complete response. This is intratumeral therapy. It should really only go into the T cells and knock down their PD1 expression. So early phase but interesting. - Interesting. This intratumural stuff is gonna be cool. It's gonna be cool to see how good they can get it to be. Excited about the varicose got one come in. We did the, we talked about the septal, sept. - Slymiclamab. - Slymiclamab one. I feel like my grandfather now. My grandfather could never say the word hippopotamus. I can't say the name of any of the drugs now. He'd be, but hips, hips, hips. Now I'm doing the same thing. - Now that's you. - And that's true. It's in the genes. So that's it. So for our listeners, you are now caught up on the real nitty gritty of everything interesting that happened at the AAD this year. These everything interesting that happened with the data for the drugs. I mean, there was a lot of interesting stuff that happened with me after 9 p.m. but in terms of the drugs you're all cut up. - All right. I wanna thank our listeners for joining us this week. Learned a few things. Hope you laughed once or twice. And mostly I'm hoping you're planning to join us next week. - Until then, I'm Matt Cyrus. - I'm Tim Patton. - And I'm Laura Ferris and we are Derms on drugs.