Decades of research tells us that the hormone DHT is the primary cause of pattern hair loss. But what if that's wrong? This isn't some hypothetical anymore. This is the position of a growing number of researchers, all stemming from the craziest monkey hair regrowth photos I have ever seen. Results achieved with a drug that didn't even touch DHT. Now, a similar drug made by Absi, an AI powered pharmaceutical company, is in phase 2 clinical trials to put this thesis to the test. I just interviewed the company's founder about their novel drug, their current clinical trials, their forthcoming results, which we'll get a peek at at the end of this year and whether DHT is the root cause of pattern hair loss, or if perhaps another hormone is actually to blame. One that once we adequately target might unlock unprecedented levels of regrowth. Stick around, we're going to be covering it all. And for those new here, my name is Rob English. I research hair loss. I publish and review scientific papers about hair loss disorders. I serve on the editorial board of a dermatology journal and I make videos like this for anybody who is fighting hair loss and looking for a path forward based on the evidence. This video is about the company Absi, their novel hair loss drug ABS 2011, and the hormone that that drug targets. It's not DHT, it's prolactin. We'll get into what this hormone is, how this drug works, if the hype is real, and never before released data from ABSI's founder, Shawn Mlan, who we actually interviewed for this video. We talked for 2 hours. We asked him some very hard questions. For those short on time, please skip to this timestamp for the key takeaways on prolactin and hair loss, ABS 2011, and whether I think this drug will succeed. And for everybody else, stick around. I'm about to tell you a story that is going to sound like a Hollywood hero's journey about hair. And it actually begins nearly a decade ago, not with Absai, but with another pharmaceutical company, Bear, and an experiment that got some very unexpected results and changed the trajectory of their research project for many years. Back then, Andreas Bush, a researcher at Bear, wanted to see if lowering prolactin levels might help improve a condition called endometriosis. So, his team set up an experiment in mice and injected them with a drug that Bear developed that would later be called HMI 115. We'll go deeper into this later, but at this stage, all you need to know is that this is a drug that once injected helps to lower levels of prolactin signaling in your cells. After injecting these mice, Andreas saw something unexpected. The mice who received HMI 115, the ones who had lowered prolactin activity, they actually saw faster hair regrowth compared to the mice who received a placebo injection. And so he took these findings to bear and said, "I think we might have something here. I think we might have a candidate for a hair loss treatment." Now, you might be thinking at this stage, big deal. And I actually agree because everything regrows hair on mice. peppermint oil, copper peptides, sugar molecules. And more often than not, those same interventions inevitably fail to regrow hair appreciably in humans because mice are not men. Mice don't naturally develop male pattern hair loss. And genetically spliced mice made to mimic that condition, they even still remain terrible proxies for treatment success because candidly, we don't even know all the genes involved in male pattern hair loss to begin with. For more information, watch our video on evidence quality. Suffice it to say that mouse models rarely translate to human success with respect to androgenic alipcia treatments. But there is another animal that isn't a human and it does naturally go bald. Stumptailed macak. And while monkeys also aren't men, they tend to fare a bit better, at least as surrogates for research translatability doing treatments on hair loss. And Andreas felt that his mouse model results were strong enough that he convinced Bear to commission a study on stumptailed macaks, inject them with prolactin receptor antibodies, monitor to see what happens with their scalps, and see if there truly might be something here. And this is where things get a little wild because after 6 months of treatment, the monkeys, they appeared totally fine. So, no issues related to adverse events that we know about except they had regrown a ton of hair and all by suppressing prolactin signaling in cells, not by touching DHT. And not only that, but when the monkeys actually were withdrawn from treatment, they were monitored for an additional 4 years. And to everybody's shock during that time period, they actually continued to regrow hair. And not only that, but the older monkeykey's hairs that had turned gray had actually repigmented. They went from gray back to colored. And why do I find this crazy? Because in all other monkey and human hair loss research that I have ever seen. I've first never seen this level of regrowth for hair recovery. And I've never seen this level of hair repigmentation. And in all other monkey and human hair loss research, when a treatment is officially withdrawn, you inevitably lose all the hair that you've regained. But in this study, the opposite happened. Despite the monkeys having stopped treatment, they continued to regrow hair more and more. They continue to get better hair pigment better and better. That is crazy. And it's something to get really excited about. And it was these findings that prompted Bear to license their drug to Hope Medicine and expedite studies in humans. In 2023, a phase 1 and phase 2 clinical study was launched. And for the next 12 months, everyone, including me, waited for the results, thinking this might be it. This could be the breakthrough everybody has been waiting for. This could actually be the thing that takes somebody from nearly fully bald to fully haired. And then nothing, nothing, nothing at all. In 2024, that research group announced that the phase 2 clinical studies had been completed. And then the company never even bothered submitting the results of the report. And then in 2025, a press release was issued about the phase 1 human study on HMI 115 on a whopping 16 people. The findings, it appeared safe, but it only regrrew about 14 hairs per square centimeter. That's a far cry from the 100 plus hairs per square centimeter on average seen in that monkey study. And all of a sudden, enthusiasm surrounding HMI5 and even prolactin's role in hair loss all but collapsed. Well, all except for maybe one person, and that was Andreas Bush. He contended that the hypothesis on prolactin and hair loss still could be right, but that the monkey study did not translate to the humans not because of differences in hair loss pathology, but instead because he thought the humans were underdosed, that their prolactin wasn't adequately reduced in the way that it was for the monkeys, and that the pharmacocinetic data later released by Bay Pharmaceuticals, according to him, actually proved it. And this is where Andreas Bush's journey moves from Bear to another company, ABSI, and from HMI 1115 to a partnership with Absi's founder, Shawn Mlan, and his research team to develop a better drug, one that fixed the problem in the original study on HMI 115, and one that would finally put to rest the thesis about prolactin and whether it was actually at the root cause of hair loss. And this is where our conversation with Shawn Mlan begins. I'll present this interview in two stages. First, I'm going to get out of Shawn's way. He has a compelling case to make about prolactin's role in hair loss, ABS 2011, their ongoing clinical trials, and that steelman argument deserves to be presented uninterrupted. And only after that will I then show you my questions to Shawn and how that altered aspects of our discussion. Prolactin has maybe had a a bad rap and I think it was just due to uh the naming you know prolactin is you know prolactation everyone thinks of it as a uh lactation hormone or or in women's health but what you see is that u prolactin is expressed all throughout the the body both in females but as well as males. You you actually see it in in the scalp. You see it in the the your joints. Uh you you see it in in in your heart. Uh in your bones it and it and it plays a really interesting uh role. >> Sean is describing our evolving understanding of the hormone prolactin. Originally only seen as a female hormone. Researchers have now found that prolactin is actually all over the body in men and in women. And its role in human health is not just relegated to lactation. It looks like it sits on this uh stress inflammatory uh axis, you know, in diseases like indometriosis um or even androgenic alopeesia. It's driving uh you know, in inflammation. Essentially, we have new work that hasn't been published yet, but it looks like, you know, it does have a role in in in metabolism. I think we're just starting to realize how important um prolactin's uh role is in in both male and females and you know in in the role of you know androgenic alipcia, autoimmune diseases uh and uh and and just kind of immunology in general. So Shawn sees prolactin as a hormone that's often elevated in conditions linked to inflammation, endometriosis, potentially some metabolic disorders, even androgenic alopecia. And at this stage, it's important to understand how prolactin is even arriving to these sites in the first place. Well, first, prolactin is made by our pituitary gland. That's the p-sized organ that sits at the base of our brain. And that prolactin will enter our bloodstream and then travel through a highway network to other places in the body where it can then attach to other organ sites and begin to influence the behavior of those cells. But according to Shawn, that's not the only way that our bodies make prolactin. There's also prolactin that our own organs can manufacture on site. And it's this production of prolactin that varies wildly in individuals. And it means that two people can have the same exact levels of blood prolactin, but then if you actually look at their tissue levels, they can be wildly different. So you have the classical pituitary um expression of of prolactin. Uh but then you also additionally have and and a lot of people don't un or or know this is that prolactin sits on a uh an additional promoter that controls the extra pituitary um uh expression. And so you could have normal systemic levels of prolactin that come from the pituitary, but an increased level of prolactin uh within the scalp and and it's being driven off of that extra pituitary promoter. And what's really interesting is that the transcriptional uh uh factors that that drive the extra pituitary u expression are completely different than what you see in um in the pituitary. So they're completely uh independent and I think that that's why for a long time this hasn't come up as a um potential you know prolactin being a potential cause of of hair loss cuz we've been looking at at you know systemic blood levels uh versus looking at what is the the actual expression within the scalp and you can have really high expression in the scalp but have completely normal um prolactin levels. One of the things though that we don't really know is that how does systemic prolactin uh in addition contribute to what's being locally um produced as as well. That's one of the um you know factors that we we still don't quite understand. >> Okay. So we see elevated levels of prolactin in organs affected by inflammation and autoimmunity. But just because something is higher in a diseased organ, that does not mean that the thing that's elevated is causing that disease. For a perfect example of this, look at blood levels of C reactive protein or CRP. CRP is often elevated in people with actively evolving atherosclerosis. And so researchers once wondered if CRP was actually causing that atherosclerosis. But later research was able to tease out that this wasn't the case. That CRP was elevated as a reaction to other inflammatory processes. In other words, it wasn't a cause of the inflammation. It was an effect. it was a surrogate of the inflammation happening. So in that same vein, what exactly is the evidence that causally links prolactin to androgenetic alipcia? Because I have to be honest with you, at first glance, the idea of prolactin causing androgenetic alopecia sounds crazy because the name of the condition describes its causes. Androgens, male hormones like DHT, and genetic, your genes. And it's not like somebody just gave this condition this name and called it a day. These causes were established over 100 years of research. Men who can't produce the hormone DHT, they never go bald. When you expose balding, sensitive scalp skin to DHT, it damages the hair follicles. And when you lower DHT levels in balding men with drugs like finasteride or dutastasteride, 80 to 90% of them will see a slowing, stopping, or partial reversal of their hair loss with results sustaining for decades. So you have decades of observational, mechanistic, and interventional data that all converge on the hormone DHT causing this condition. So where on earth does prolactin fit into this? And interestingly, Shawn doesn't refute DHT's role in androgenetic alopecia. He thinks it's absolutely causal. He just argues that DHT doesn't just magically appear in balding scalps. It increases in part because of prolactin. And not only that, but by targeting prolactin, he thinks we might even be able to overcome some of the biggest hurdles that prevent people from getting huge hair recoveries even after they lower their DHT. The name is actually very misleading, androgenic alipcia. It implies that it's androgen driven. Yes, androgens are a part of it, but from what we're seeing, prolactin actually sits potentially upstream of the androgen receptor. And we actually even have data that that does show that um prolactin drives uh increase in androgen uh transcript and and so it does look like it regulates uh the androgen receptor. There's a lot to unpack here, but basically Shawn is suggesting that when prolactin arrives to a balding scalp, it activates androgen receptors, which are what cells use to allow hormones like DHT, to attach to those cells and then exert their effects. And if I were to brutally simplify the old guard versus new guard or new hypothetical argument for androgenic alipcia, the old argument looks like this. after you hit a certain age, your genetics will cause DHT levels to rise in the scalp, and those DHT levels will then cause pattern hair loss. What Sean is saying, it adds a a step right here and a step right here. So, it doesn't nullify decades worth of data. It just adds steps to what's happening and makes the chain of events a little more specific. So, that is the supposition. But what is the evidence to support that supposition? In our interview, Shawn builds his case starting with observational data on genes, prolactin, and severities of balding. What we did here was we we took a look at the uh UK bio bank and uh evaluated um how changes in prolactin uh expression or prolactin receptor expression uh changed the the uh the outcome of of balding. And and what we saw was was really really uh pretty uh uh remarkable was that in those that were not balding or had very little balding, they had much lower prolactin receptor uh levels. And those individuals that had, you know, moderate to severe balding, you saw uh an increase in the overall um prolactin receptor uh expression. >> So to reiterate, Sean's team took genetic data from over 165,000 men in a database and then he focused an analysis on genes that control for prolactin receptor expression in cells. Now, some genes will relate to more prolactin receptor expression, others less. And then his team compared those genes to the men's self-reported severities of hair loss. Zero being no hair loss, four being severe hair loss. And they found that men with little to no hair loss also happened to have genes linked to lower prolactin receptor expression. And men with lots of hair loss had genes linked to higher prolactin receptor expression, which they also plotted in this chart. The thing that's pretty remarkable about this is these are like very very small changes in prolactin receptor expression. Uh and by very small changes, you're still able to actually see an effect in in male pattern baldness. Uh you know, these aren't massive changes in in overall expression, just minor minor changes. But we know that association doesn't equal causation. Ice cream sales are linked to shark attacks, but ice cream sales do not cause shark attacks. The confounder is the warm weather getting people to buy ice cream, but also to go to the beach and also into the ocean. So observation by itself is not enough. And then we have to ask what else is there that might causally link prolactin to androgenic alopecia. Well, even before Absai and Bear thought to target prolactin for androgenic alopecia research, Shawn actually told me about a research paper from 2006 by Ralph Paws and it showed in biopsies of human hair follicles that hair follicles could make prolactin on site and that prolactin could also trigger those hairs to shed. So that's a little data, but more interesting is some of the mechanistic work that Shawn and his team later did to start to tease out cause and effect between prolactin and balding. Some of which has not yet been made public until this interview. What we did here was we actually took uh human uh scalp biopsies uh of both male and female and what I'm showing here is is male and we then um cultured it in uh with ABS 2011 uh which is uh our antiproactin receptor um blocking antibbody and uh additionally uh um cultured it with prolactin and then had a rescue arm where we added both prolactin as as well as uh ABS 2011. And uh what you see here is uh how much hair uh was grown uh in a 3-day um period. And this is, you know, the the same um type of measurement uh that is actually going to be done uh in uh the clinical study uh looking at um the photography and seeing how much uh hair was actually grown. And you can actually see here um within a 3-day time period, ABS uh 2011 was able to uh increase hair growth uh and you you you saw more hair follicles go into the uh antigen state and um prolactin um when you added it uh essentially shunted the overall growth. And by adding both prolactin and uh the the receptor uh uh or and and the antibbody, you're able to rescue uh the the follicle. >> So here Sean's team took scalp biopsies from three balding men. And then they exposed their skin to either nothing at all or their prolactin receptor antibbody drug ABS 2011 or more prolactin or more prolactin plus ABS 2011. 3 days later, the samples exposed to ABS 2011, they grew longer hair and they still had more of their hairs in the growth phase of their hair cycle than the samples that were left untouched or given more prolactin. The implication from this Xvivbo research is that blocking prolactin might improve hair parameters in scalpkin samples of androgenic alopecia. Now, this is great and all, but growing longer hair or having hairs shed less frequently does not explain what happened in these stumptailed macaks. These monkeys saw near full hair regeneration and near full hair repigmentation. This is a level of recovery that simply does not happen in humans with androgenic alopecia. It also is very rare to see in other monkey studies as well. In fact, in humans in specific, studies show that if you take your DHT as low as you can or you stimulate hair growth with drugs like minoxidil, on average, the best that you can expect is that you'll be able to rewind the clock on how your hair looks by around 6 months to 36 months. That's an average. Some people do a little bit better, some people do a little worse, but after that point, it's like people hit a wall. You just don't get more hair back. And the question is why? And at least so far, researchers have identified three possible reasons. First, when you have advanced stages of hair loss, hair follicles will develop scarring or paraphilicular fibrosis. And this might act like scaffolding that inevitably blocks hairs from shedding out and then resizing as thicker. So, in this case, you can reduce the DHT all you want. You can stimulate the hair to grow all you want. But if you don't get rid of that scaffolding, you're not going to be able to allow for the hairs to resize as larger in subsequent hair cycles. Second, after hairs become miniaturized beyond a certain point, research suggests that they become detached from their goosebump muscle. That's the erector pilli muscle. And research so far seems to show that while we can save hairs that haven't yet detached from that muscle, we've not yet reliably seen evidence that any treatment available today can reattach hairs that have detached from their erector pilli. So hairs that are miniaturized beyond a certain point just don't seem to be able to be saved. And again, reduce all the DHT you want, growth stimulate all you want. If you can't get that attachment back, you're not going to recover those hairs. And the third possibility is that at some point in the balding process, hair follicle stem cells which tend to be preserved even in advanced stages of hair loss, they start to lose their ability to convert from stem cells to other cell types like progenitor cells. And this failure step is why current treatments might not yet be able to fully revive those miniaturaturized hairs. And so for a prolactin receptor antibbody to do something like this in humans that's not coming from hair elongation. It's not coming from a longer growth stage of your hair cycle. That's quite literally hair regeneration. It's taking a fully vevelis hair and returning it to a fully terminal hair in many cases. It's solving somehow one of these rate limiting regrowth factors that we know about in androgenic alopecia. And so I asked Shawn about this and if his team had thought about this and it turns out they had. And not only had they thought about it, but they had run an experiment and they think they might actually have identified which of these rate limiting recovery factors their treatment could address. It's the stem cell failure. >> One of the big things that that you see uh with uh balding individuals is that they lose their progenitor uh uh cells over time. Um and as you slowly lose those over time, you get more and more uh miniaturization uh that that occurs. some of the data that that we generated um where we were able to see that uh ABS um 2011 uh is able to uh actually increase um the the proliferation of the K15 uh stem cell um population uh and it prevents the apoptosis uh which is is really great to to see. You see prolactin on on on the right hand side uh does drive um apoptosis of the uh K15 uh stem cell. And what's also uh really quite interesting is uh the progenitor uh cell line. What we see is the uh CD34 cells um are are decreased um when you add prolactin uh to these uh Xvivo u uh models. Again, these are human um um scalp biopsies. And so we do believe that blocking prolactin receptor uh is is able to at least um um uh keep the K15 stem cell population where it is and and be able to stop uh the uh CD34 uh stem cell population from further uh uh depleting. So we we do think that there is this this ability to actually have a regenerative uh effect here. Currently there is no therapy that is able to reverse that that that stem cell niche and you know potentially be able to reverse uh the the miniaturaturization and this is where we think ABS 2011 uh could have a a big role here. Sean is saying that this mechanistic data suggests that if we block prolactin with ABS 2011, we might also be able to stop hair follicle stem cell degradation, improve their differentiation into other cell types, and that we might be able to overcome this rate limiting regrowth factor that other hair loss medications that exist today have failed to address. And that's how we might be able to explain these monkey results. But he also went a step further and he shared data not yet released in any public setting that he feels further corroborates this hypothesis. >> One of the phenotypes that has been shown is that uh collagen 17A uh decreases over time with the the stem cell uh population. And collagen 17A is really important uh in the sense that that is what anchors the stem cell population uh to the to the actual hair follicle itself. And what you see is that this gets degraded uh over time. And so the fact that you're actually modulating the stem cells in addition to increasing collagen 17A when blocking the the prolactin receptor uh is is really quite encouraging and and showing that indeed prolactin may sit up you know uh you know you know pretty far upstream where you know prolactin is is driving the the degragation of the stem cell niche. it, you know, it uh, you know, drives uh, it doesn't replenish the collagen 17A and then it's it's driving the the inflammation that that you see as as well. And so, uh, we we are encouraged to uh, see again this is a a 6 day uh, culture. So, you you have to kind of take it for what it is, but it is a human biopsy. And the the fact that we are seeing results in 6 days is is really incredible. The fact that you're actually regrowing the the hair, showing what prolactin does, you know, showing uh how prolactin uh is driving some of the same phenotypes that that we see uh in in prior research is is is really quite exciting. And so you're you're hitting on kind of a a whole different mechanism that both minoxidil as well as uh the you know androgen receptor uh um u you know mechanisms are are unable to uh to to to ultimately address. >> So there it is. That's the hypothesis around prolactin and androgenic alopecia. In balding hair follicle sites prolactin begins to increase. This causes a whole cascade of events. In one cascade, prolactin might increase androgen receptor expression, which then increases DHT, which then damages the hair follicles, causing them to shed prematurely and then come back miniaturaturized in the next hair cycle. And simultaneously, in another cascade, prolactin may degrade collagen 17A, which anchors the hair follicle stem cell bulge to the hair follicle itself. And with enough degradation, this then prevents the conversion from hair follicle stem cells into progenitor cells, which then limits our ability to regenerate hair that's already fully miniaturaturized, especially with DHT reducing treatments like finasteride or dutastasteride or even some treatments for females that are more powerful androgen receptor antagonists like spironolactone, flutamide, and bicolutamide because these things they only target part of the equation that Shawn proposes. But by blocking prolactin from reaching the hair follicle at all with a prolactin receptor antibbody like ABS201, Shawn argues that both of these disregulation cascades might get addressed and that because we're addressing both simultaneously rather than just one and we're targeting something further upstream than just DHT, these crazy monkey regrowth results all of a sudden might become a reality for people. And with this model, the monkeykey's continued hair regrowth even after quitting treatment becomes at least partly explainable because once those stem cell bulge connections are reestablished, hairs might just keep getting thicker and thicker in subsequent hair cycles regardless of whether you're continuing that treatment because it also takes time to build them and it takes time to degrade them as well. So, it's an enticing hypothesis, but then if the hypothesis is even true, why did HMI 115 fail to regrow hair appreciably in humans? I mean, it barely got any regrowth. Well, this is where Andreas Bush, the man who ran the original HMI 115 studies in monkeys, teams up with Shawn and proposes a datadriven conviction. The hypothesis on HMI 115 and prolactin was not wrong. the humans in the study were simply underdosed. And it's this very premise that led Andreas Bush, Sha, and Absai to develop a new drug and rerun this hair loss experiment in humans in what's currently a phase 2 clinical trial going on right now. Now, here's what Shawn had to say about the differences between HMI 115 and ABS 2011. There are a lot of technical terms here. I will stop and explain them as we go, but this is the core thesis behind what Sean's company hopes will become a billiondoll drug. >> What you saw in the stumptails was 90% receptor occupancy and what you saw from the HMI115 data from the P. So they they publicly released the PK data and then we modeled the RO based off of of that. And it's it's really quite quite uh uh shocking and uh I think you'll you you'll see why we're quite confident in the profile that we have. >> Okay, so what is Shawn talking about? 90% receptor occupancy PK data. What does all this mean? Well, first Shawn is referring to what he describes as publicly released pharmacocinetic data on HMI 115. PK stands for pharmacocinetics. That's basically just the study of how a drug behaves in your body, where it goes, how long it stays there, that kind of stuff. And what Sean is saying is that in this study on monkeys, HMI 115 was able to block 90% of those monkeys prolactin receptors. In other words, HMI15 achieved 90% receptor occupancy. And this is important because the more prolactin receptors occupied by HMI 1115, the less that prolactin can then attach to that cell and the less that prolactin can then affect it. So the more that you block, the less prolactin will have as an influencer on that cell's behavior. And at least in this monkey study, when you hit 90% receptor occupancy for prolactin, it seems to be doing some really impressive things. But this is the critical point that Sean is about to make. >> What's really interesting about the prolactin receptor is that you have to block it pretty substantially in order to completely block it. What do I mean by this? even if you're at let's say 60 uh 70 even you know 80% um receptor occupancy you could still have full activity of the the actual um pathway until uh you block it um you know substantially. >> Now what Sean is talking about here is a concept known as receptor reserves or spare receptors. Basically, this is a biological phenomenon where for certain hormones, your cells will express a ton of receptors to capture them such that a majority of those receptors that are active probably aren't even needed. They're considered spares. One of the most dramatic examples of this is with the hormone insulin. In muscle cells, you can have 100 insulin receptors available. And yet, insulin only needs to attach to one of them to exert its maximal metabolic effects on that muscle cell. In other words, it doesn't matter if insulin attaches to just one receptor or 99 of the receptors. The cell's behavior does not change after one. So, if you wanted to create an insulin receptor blocker that was effective, you'd literally need to find one that blocked as close to 100% of insulin receptors as possible. Because if the blocker only blocks 99% of them, that medication has zero effect. And it turns out this same receptor reserve relationship may also exist with prolactin. For instance, in one study on lymphoma, prolactin hit its maximal effect on cell growth at just 35% receptor occupancy. So you could be at 35% or 100% and the same growth trajectory occurred. And what this means is that if you made a prolactin receptor blocker that blocked a whopping 65% of prolactin receptors, well, in this lymphoma study, your prolactin receptor blocker would still be 100% useless. In fact, in that study, even if you blocked prolactin receptors by 80%. You'd still see prolactin exerting more than 90% of its maximal growth effect on those cells. So, think of it like failing a test. It doesn't matter if you got a 59 out of 100 or a one out of 100, you're still getting an F. And so now the question becomes with HMI 115 these monkeys were suspected to hit 90% receptor occupancy RO but did the same actually happen in the human clinical trials according to Sha and Andreas Bush the answer is no. What you see from HMI5 data here again this was they publicly disclosed what the PK profile was in their phase one. We then modeled out what the RORO um would be based off of the the publicly available data. And you you see that uh it takes quite a bit of time uh for the HMI115 molecule uh to actually uh ramp up to um you know roughly 70% uh receptor occupancy is is the the CAX or 72 73 and it then oscillates. Now what's the significance of the oscillation? So when you block prolactin receptor, you actually get an increase in prolactin levels. And if you then dip below a certain receptor occupancy threshold, you could actually be activating the the prolactin receptor with the increased levels of prolactin that are in the system. So you're inadvertently going in between antigen and kadagen. antigen, kadagen, antigen, kadagen. And we know that it takes time to rebuild the stem cell niche. And you need a sustained uh level of receptor occupancy for a long period of time uh to be able to rebuild that stem cell niche. And we believe this is the reason why uh HMI115 did not uh achieve the the full efficacy because they they weren't able to give the hair follicle kind of a long enough time to uh actually rebuild that stem cell niche um because it was kind of constantly oscillating in and out of antigen and and kadagen um phase versus you know what you see with with our molecule is that you get uh sustained the levels of greater than 90% receptor occupancy for for 6 months uh straight. Uh and and and we're above the 90% receptor occupancy which again is what you saw in in the stumptail macak and again we believe in the mechanism based on everything we've we've told you. It just came down to a PK and dosing issue with HMI115. So now you have the core thesis behind ABS 2011. Andreas, Shawn, the broader ABSI team, they developed this drug to solve for this receptor occupancy problem. And their phase 1 and pharmacocinetic studies according to Sha prove that ABS 2011 achieves a prolactin receptor occupancy level of greater than 90%. That's a lot. And being above that 90% receptor occupancy threshold according to Shawn through inferences in this monkey data is the level that you need to adequately suppress prolactin levels in hair follicles which with sustained suppression will hopefully give the stem cell bulge enough time to rebuild which is what we need to achieve truly regenerative effects in humans. And it's this very premise that guided Shaun's team through pre-clinical work, then phase one human studies for safety, and now a phase 2 human study on men and women with androgenic alopecia. And this, Shawn believes is the test that we need to truly ascertain if this hypothesis surrounding prolactin and hair holds validity and if this treatment target might be the breakthrough the entire hair loss community has been waiting for. This phase 2 study, it is already underway and in December of this year, Shawn and his team plan to do a preliminary 13-week read and an announcement of the data. >> The 13we data readout that's going to come in December. We have not given firm metrics on what we would like to achieve there. We have talked about it being directional. We want to see that the mechanism is is is working and that there is kind of a path to uh 30 plus hairs per square centimeter at at 26 week. And so I think that we have set ourselves up in a way that again this is a more an exploratory look at how the mechanism is is performing uh to to date. Uh, additionally, we do feel good about the readout at at 26 weeks, but let's say we achieve 30 plus at at 26 weeks. My guess is that 9 12 months, you continue to see an increase uh from from there. Um, but you know, we are confident that you'll see, I think, strong or good results at at at 26 weeks, but that doesn't take away from the fact that you could continue to see uh hair regrowth past uh 6 months. And and the great part about that is we are actually going to be tracking these patients for a year post uh treatment. So we are going to understand like how the you know uh how how the changes are are progressing over over that year um post treatment. So I think that that'll also be a really exciting uh insight that we're going to see as well. >> And here's the part that I really appreciated about my conversation with Shawn. So I voiced to him about how frustrated I've been this year and last year with all of the press releases from other companies that are pursuing future hair loss treatments. The through line here is that there is a massive amount of data withholding, manipulation of statistics, disingenuous comparisons across hair count groups, subgroup of subgroup analyses, the absence of reporting and critical metrics like absolute terminal hair count changes. And so I just asked him directly that regardless of these 13week results if it would be possible if he could commit to just not pulling any of these weird statistical stunts or obscurities in the way that data is reported. And here is what he said. I can promise you that we will have a non-controversial data cut. We are not going to do a sub population of sub population like it. It's going to be clear-cut uh data that will be uh easy to to interpret. >> And that to me is amazing news. So kudos to Shawn for this. And in December or January, you can bet that I'll be making a follow-up video about that press release and the data. I hope that it is fantastic. So this about wraps the Steelman case for prolactin, its role or potential role in androgenic alopecia, HMI 115, why it supposedly failed, the evolution to ABS 2011, and how lowering prolactin might unlock near full levels of hair regrowth. And I really want to present Shawn and the broader data here in the strongest way possible. I wanted to slow down the storytelling to reiterate information that was key to add support where I could because he reached out to us. He gave me a ton of time. We had two calls. The first one was an hour. The second one was 2 hours. He's committed to giving public and uncontroversial reads of ABS 2011's 13week data. And that part of the discussion here deserves to stand alone without my interruptions, without my nitpicking, because it truly is a service that Shawn took the time to do this. But I obviously asked Shawn a ton of questions during our conversations because I wanted to improve my clarity on the strengths, but also the limitations of the evidence presented. And in this respect, I always think that we should remain hopeful about future treatments and the work going into them. But in general, it usually helps to have a precaution to temper expectations about what a clinical trial is going to do. Because as it stands, I think the data around prolactin and hair loss is compelling in some respects and limited and potentially conflicting in others. And I'll get into that level by level right now. First, let's start off with HMI15's monkey data. The results are absolutely incredible. I mean it when I say that I've never seen monkey results to this degree and the continued hair regrowth post treatment withdrawal, I have never seen that in any androgenic alopecia study, monkey or human before. But is this magnitude of regrowth truly unrivaled in monkey studies? Not necessarily. While it's not the same recovery, take a look at this study on stumptailed mac and minoxidil. In humans, topical minoxidil tends to produce relatively modest hair gains. The cosmetic results tend to peak around six to eight months and then you plateau and even slowly decline thereafter. But in this monkey study, the monkeys using minoxidil, they just kept regrowing hair. They regrrew hair at month three, at month six, and at month nine. In fact, they kept regrowing more and more hair all the way up until they withdrew from treatment. So these monkey models can directionally translate to humans with androgenic alopecia, but they're not perfect surrogates by any means. In fact, in my opinion, I think that reconverting vellis hairs into terminal hairs in monkeys is just a ton easier than it is in humans because the treatments that seem to do it in monkeys like minoxidil, when you apply those to humans, you don't get the same results. You get the same direction in results. You don't get the same magnitude of results. And it's not just minoxidil. We've also seen the magnitude of results really decrease with other treatments when Latanoprost or Bataprost moved from monkey models to humans. They went from pretty impressive results to very tiny, ambiguous, and cosmetically insignificant results. So again, we have to temper our expectations. What we see in these monkeys directionally might fit with humans, but the magnitude of impact, it might be very tiny. We don't know yet. Next, let's talk about this genetic data that Shawn presented. Now, Shawn showed us some charts suggesting that genes linked to higher prolactin receptor expression were also linked to higher severities of balding. And Shawn noted in the interview that all it took were just tiny differences in prolactin receptor expression to show this relationship in the severities of balding. However, this observational relationship to me appears somewhat at odds with the idea that prolactin is a hormone with high spare receptors or receptor reserves. So, for instance, if this gene for prolactin receptor expression is linked to little to no hair loss, but this gene is linked to a ton of hair loss, and yet the difference in prolactin receptor expression across the genes is maybe 10, 20, 30, 50, 70%, even if it's 80%. Then what difference does that make if all prolactin needs to do to trigger hair loss is occupy 10% of those available prolactin receptors? With such a low threshold for prolactin to potentially have these adverse hair effects, wouldn't that imply that micro differences in prolacter receptor expression shouldn't matter at all that instead we would want to see 10 or 20fold differences in expression activity before we start to see these problems? And yet, we can't really answer these questions right now because the data is so preliminary, but it's also really limited. Next, let's talk about some of the Xvivo data that Shawn presented. These studies on balding hair follicles are great mechanistic tools for research. But the one relationship that they don't establish is if all these same directional relationships with hair also exist in nonbalding scalp hair. Because if prolactin also does all the same exact things at the same exact magnitude, it stops hair elongation. It turns hairs from growing into resting. If it does that the same in balding hair samples as it does in non-balding hair samples, then this would actually weaken the case for prolactin causing androgenic alopecia. So I asked Sean about this in the interview and if they had done experiments with non-balding human scalp hair as well. And here was his response really quickly. So we can see that there's some degree of significance with those effect sizes on the slides you just showed. Those are from three male scalp biopsies with androgenic alipcia. Do you have control data on a scalp unaffected by androgenic alipcia as a comparator of any type? >> Uh we do not. We took it from an androgen sensitive uh area uh which is the frontal temporal uh uh region. Um but we did not have a uh healthy or a um non uh um you know balding sensitive uh uh area. Um so so we currently do not have that at the moment. >> Okay. Yeah. I'd be really curious to see if you see the same exact drops in an unaffected AGA scalp skin sample as well because then that would help to tease out whether or not those drops are truly relevant to the mechanisms being explored. >> Yeah, absolutely. And uh one of the things that I think we'll we'll we'll see uh actually before we even get data like that is actually how this performs in in in humans later this year. >> Now, for what it's worth, Sean's reply here is fair. You could spend your whole life running XVivo studies trying to guess what happens in a human. Eventually, you just need to prove safety as best as you possibly can and move on to human testing. But without those non-balding control samples, I personally don't find this mechanistic data nearly as compelling. And the same criticisms apply to research presented about collagen 17A. It's a fascinating hypothesis. New research indicates this could be a critical piece to the balding process and a rate limiting recovery factor with respect to androgenic alipcia treatment success. But without knowing how non-balding hairs also react and also express collagen 17a, we can't actually distinguish if any increased expression or decreased expression of anything is meaningful and if it's truly unique just to balding affected skin. And this matters even more when we actually revisit that original 2006 paper from Ralph Poss. And we actually see that in that study, the effects of prolactin on human hair follicles, they were coming from nonbalding hair follicles. And yet the researchers found the same relationships. This study used occipital regions of the scalp during facelifts and hair transplant surgeries. And in both cases, those should be hairs that are relatively protected from the balding process that aren't as prone to DHT's mediating effects on androgenic alopecia. And yet, in that 2006 study, the same relationship seemed to exist with a non-balding human hair follicle as we're now seeing in the balding human hair follicle research 20 years later. Next, there's the discussion about safety, about lowering prolactin levels in cells and whether or not that's something that's safe long term. In women, hypoprololactinemmia is associated with an inability to lactate and it's also associated with infertility. Now, on their own website, ABSI sites papers to suggest that reducing prolactin is potentially very safe for many adverse events, but they mainly focus on safety metrics that are not fertility and not lactation. And because of this, I wanted to understand not only which adverse events of interest Shaun's team will be tracking in their clinical study. I also wanted to know how they were tracking the adverse events themselves. And there's a very specific reason why I wanted to ask this. I will show you the clip here. So, you mentioned Ferodmics just a second ago. I've been tracking their data as well. I think that anybody innovating and attempting to run well-designed studies in the hair loss space for interventions is incredible. So, I really appreciate what they're trying to do. When I looked at their clinical data and specifically their adverse events, I saw some things that didn't make total sense to me. So, we know that their formulation is uh a larger dose of minoxidil that is supposed to slow leak into your system over time. And when we look at all of the clinical studies on oral minoxidil ranging from 0.25 25 milligrams and higher 60 to 90% of participants both male and female across literally all of the studies report hypertriosis. And when I looked at veroddermic safety data I saw the hypertriosis numbers at something like 3 to 6% which was comparable to the placebo group. So this means that either they have inadvertently developed a hypertargeted oral minoxidil that then attaches only to the scalp and does not affect hair anywhere else on the body which is not listed in any of their patents or there is something with their data collection with respect to safety that is not adequately capturing the real risk of hypertriosis that we would expect for this medication. Which then leads me to the question about how your team in your phase 2 clinical studies is capturing clinical adverse events reporting. Are these done through interviews with the investigators? Are these done through survey systems? Are they done through open-ended questionnaires? Each of these has their pros and their cons, and there's plenty of debate as to which is the best in clinical research and reporting. But I'm curious just to get your perspective on how you are tracking these things because earlier we were talking about libido and the potential for no effect, maybe even benefit from this type of therapy, but then libido is separate from semen parameters and you can have a strong libido and be completely infertile. And so I'm just kind of curious at this point for how you guys in your phase 2 clinical research have prespecified how you'll collect adverse events and the specific adverse events that you are exploring. >> Yeah, it's a great question. So first off, we have a fantastic chief medical officer. Uh he was the the SVP and head of clinical development at Vertex. uh prior to that he was at uh uh Amgen and you know has you know 20 plus years of uh very hardcore clinical development uh experience uh you know well outside of even you know dermatology. I mean he's he's run some of the most complex and and hard clinical trials. He actually ran a you know the Draavx the the NAV uh 1.8 8 uh clinical study which is a pain study and pain studies are notoriously very very challenging and and was uh successful in in in that study and so he has brought a lot of rigor into uh ABSI on the clinical development uh side and we are wanting to make sure that uh we have a uh robust uh study uh and you know we believe with how we have set up this study uh If successful, we see this as a um potentially a a dose range finding study where we can go on to a phase three clinical study. and and in terms of like the overall clinical operations, the the protocols that that we have in in place, uh I can say that they're of the the highest uh standard and uh you know, these um you know, the questionnaires and and how they're asked, they're they're all done uh in a way to uh really help uh uh do it in an unbiased uh uh way. And and we have a really incredible clinical development team on all the specific, you know, details. uh we'd have to bring him on to to kind of go through all of those. Um but uh I I I do know though that uh it is a is a very rigorous uh study and you know you can even look at how we designed the the phase 2 um clinical study. It's a you know it's a 3:1 um um um um placebo um uh uh controlled um double blinded uh study. Uh and yeah, really excited about the the overall um uh kind of results both on the efficacy as well as um being able to ensure that the uh you know adverse um uh events are are are um recorded and and uh uh done in an appropriate manner. >> By the way, I'll link our video on vermics below if you caught that comment. But in any case, Shawn preferred in this case to defer answering this to his head of clinical development. Also, it is totally fine to do that. He's the CEO of ABSI. He's not in the weeds leading every aspect of the clinical research projects, but adverse event tracking and how it's reported is one piece of a clinical trial protocol that basically almost never gets published publicly in a repository, but that is super important to understand because the way that you collect results can drastically change the outcomes. And those differences in results don't actually reflect product safety differences. they just reflect differences in the way that data was collected and that's the issue. So perhaps in the future we can get a little bit better clarity on this and it'll be one of the things that I'd love to focus on if and when it's time to see ABS size clinical data or if we're able to connect with their head of clinical research. Next, for veterans of the hair loss community, you will know that we have reached this milestone in research for hair loss treatments many times before, where observational, mechanistic, and even early interventional data all point toward a new novel breakthrough just around the corner for androgenic alipcia only for the human clinical trial to fail miserably. One recent example, prostaglandon D2 antagonism, specifically the drug setup. Observational data found that prostaglandin D2 was elevated in balding scalps. Mechanistic data suggested PGD2 stopped hair lengthening. Monkey data on prostaglandin analoges like latannoprostatrost even to a certain extent minoxidil all showed impressive hair gains. And yet when a prostaglandon D2 inhibitor setipin was finally tested in men with androgenic alopecia there was literally no effect at all. So remain hopeful, but don't forget about the graveyard of prior prospective treatments that made it all the way to this point only to still fail a clinical trial. Statistically, it is the phase 2 human study that tends to make or break most real contenders in the hair loss treatment space. And lastly, this one I really love. Even if ABS 2011 fails, it still actually does not disprove the hypothesis that prolactin might be a root cause of androgenic alopecia. It might turn out that it's still just not powerful enough of a prolactin receptor antibbody. Keep in mind that that lymphoma study I talked about earlier, even when prolactin occupied just 7% of the available receptors, cell growth was still at 50% its maximum speed. In this respect, we might actually find that a failed clinical trial on ABS 2011 simply means that we have to build something that suppresses prolactin even harder. It's wild to think about that fact that even with ABS 2011, a drug that was designed to overcome this one liability, we still might not be able to confirm or rule out the legitimacy of the hypothesis. And that is just the way that hair loss research goes. Okay, that is everything. I know this video was a long one. I hope that you enjoyed it. I hope that you learned something. We put a ton of time into creating it and I really wanted to thank Sean for taking the time to reach out and do this interview with us. I loved our discussion. I really appreciated his time and most importantly, I want his product to succeed. I think that if it does, it's going to be an incredible compliment or even a replacement to every other treatment out there. We can only hope and time will only tell. We'll know more at that 13week data read. However, even if the results are very tiny at 13 weeks, recall that the monkeys took four years for significant hair regeneration. You can't look at the data at 13 weeks for efficacy. I think that would be a huge mistake. What we should be looking at here is whether or not the prolactin receptor antibodies are safe. What are people reporting in terms of fertility markers, libido markers, anything else that's an adverse event of interest? That is what's most important at this read. Even if hair counting data looks flat or slightly negative, I am not discouraged by that. It is 13 weeks, so give it more time. Speaking of time, if you are fighting hair loss, you have to make do with the treatments that are available today. And if you're interested in pursuing treatments that are hyperpersonalized and evidence-based, I helped co-found the brand ULO, that's ul.co, to facilitate access to those treatments. We're a US-based teleahalth brand focused exclusively on hair loss. And we deliver what I would consider an unrivaled level of personalization to make sure you're getting the best possible outcomes that respect your needs, but also your preferences. We have lowd dose formulations of topical finasteride and topical dutastride. their full strength counterparts. We have topical minoxidils paired with retinoic acid or tininoan. We offer high strength oral dutastasteride, standard dose oral dutastasteride, standard dose finasteride, and a lot of other options to help facilitate your journey. I hope you check out the brand and in the meantime, we'll keep making content like this. I hope you enjoy it. I look forward to next