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Prolactin Is THE Root Cause of Hair Loss?! Absci’s New Drug May Prove It — Transcript

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0:00Decades of research tells us that the
0:01hormone DHT is the primary cause of
0:04pattern hair loss. But what if that's
0:07wrong? This isn't some hypothetical
0:09anymore. This is the position of a
0:10growing number of researchers, all
0:13stemming from the craziest monkey hair
0:15regrowth photos I have ever seen.
0:18Results achieved with a drug that didn't
0:20even touch DHT. Now, a similar drug made
0:24by Absi, an AI powered pharmaceutical
0:26company, is in phase 2 clinical trials
0:29to put this thesis to the test. I just
0:32interviewed the company's founder about
0:34their novel drug, their current clinical
0:36trials, their forthcoming results, which
0:38we'll get a peek at at the end of this
0:40year and whether DHT is the root cause
0:42of pattern hair loss, or if perhaps
0:45another hormone is actually to blame.
0:47One that once we adequately target might
0:50unlock unprecedented levels of regrowth.
0:52Stick around, we're going to be covering
0:53it all. And for those new here, my name
0:55is Rob English. I research hair loss. I
0:57publish and review scientific papers
0:59about hair loss disorders. I serve on
1:01the editorial board of a dermatology
1:02journal and I make videos like this for
1:04anybody who is fighting hair loss and
1:06looking for a path forward based on the
1:08evidence.
1:13This video is about the company Absi,
1:16their novel hair loss drug ABS 2011, and
1:18the hormone that that drug targets. It's
1:21not DHT, it's prolactin. We'll get into
1:24what this hormone is, how this drug
1:26works, if the hype is real, and never
1:28before released data from ABSI's
1:30founder, Shawn Mlan, who we actually
1:32interviewed for this video. We talked
1:34for 2 hours. We asked him some very hard
1:37questions. For those short on time,
1:38please skip to this timestamp for the
1:41key takeaways on prolactin and hair
1:43loss, ABS 2011, and whether I think this
1:45drug will succeed. And for everybody
1:48else, stick around. I'm about to tell
1:50you a story that is going to sound like
1:52a Hollywood hero's journey about hair.
1:55And it actually begins nearly a decade
1:57ago, not with Absai, but with another
1:59pharmaceutical company, Bear, and an
2:02experiment that got some very unexpected
2:04results and changed the trajectory of
2:06their research project for many years.
2:12Back then, Andreas Bush, a researcher at
2:15Bear, wanted to see if lowering
2:17prolactin levels might help improve a
2:19condition called endometriosis. So, his
2:22team set up an experiment in mice
2:23[music] and injected them with a drug
2:25that Bear developed that would later be
2:27called HMI 115. We'll go deeper into
2:30this later, but at this stage, all you
2:32need to know is that this is a drug that
2:34once injected helps to lower levels of
2:37prolactin signaling in your cells. After
2:40injecting these mice, Andreas saw
2:42something unexpected.
2:44The mice who received HMI 115, the ones
2:47who had lowered prolactin activity, they
2:49actually saw faster hair regrowth
2:52compared to the mice who received a
2:53placebo injection. And so he took these
2:55findings to bear and said, "I think we
2:58might have something here. I think we
2:59might have a candidate for a hair loss
3:01treatment." Now, you might be thinking
3:02at this stage, big deal. And I actually
3:05agree because everything regrows hair on
3:08mice. peppermint oil, copper peptides,
3:11sugar molecules. And more often than
3:13not, those same interventions inevitably
3:16fail to regrow hair appreciably in
3:18humans because mice are not men. Mice
3:21don't naturally develop male pattern
3:23hair loss. And genetically spliced mice
3:26made to mimic that condition, they even
3:28still remain terrible proxies for
3:30treatment success because candidly, we
3:32don't even know all the genes involved
3:34in male pattern hair loss to begin with.
3:36For more information, watch our video on
3:38evidence quality. Suffice it to say that
3:40mouse models rarely translate to human
3:43success with respect to androgenic
3:44alipcia treatments. But there is another
3:47animal that isn't a human and it does
3:49naturally go bald. Stumptailed macak.
3:52And while monkeys also aren't men, they
3:55tend to fare a bit better, at least as
3:57surrogates for research translatability
4:00doing treatments on hair loss. And
4:01Andreas felt that his mouse model
4:03results were strong enough that he
4:05convinced Bear to commission a study on
4:08stumptailed [music]
4:08macaks, inject them with prolactin
4:11receptor antibodies, monitor to see what
4:14happens with their scalps, and see if
4:16there truly might be something here. And
4:19this is where things get a little wild
4:22because after 6 months of treatment, the
4:25monkeys, they appeared totally fine. So,
4:27no issues related to adverse events that
4:29we know about except they had regrown a
4:32ton of hair and all by suppressing
4:35prolactin signaling in cells, not by
4:38touching DHT. And not only that, but
4:40when the monkeys actually were withdrawn
4:42from treatment, they were monitored for
4:44an additional 4 years. And to
4:46everybody's shock during that time
4:48period, they actually continued to
4:50regrow hair. And not only that, but the
4:53older monkeykey's hairs that had turned
4:55gray had actually repigmented. They went
4:57from gray back to colored. And why do I
5:00find this crazy? Because in all other
5:03monkey and human hair loss research that
5:05I have ever seen. I've first never seen
5:08this level of regrowth for hair
5:09recovery. And I've never seen this level
5:11of hair repigmentation. And in all other
5:14monkey and human hair loss research,
5:16when a treatment is officially
5:18withdrawn, you inevitably lose all the
5:21hair that you've regained. But in this
5:23study, the opposite happened. Despite
5:26the monkeys having stopped treatment,
5:28they continued to regrow hair more and
5:30more. They continue to get better hair
5:32pigment better and better. That is
5:34crazy. And it's something to get really
5:36excited about. And it was these findings
5:38that prompted Bear to license their drug
5:41to Hope Medicine and expedite studies in
5:44humans. In 2023, a phase 1 and phase 2
5:47clinical study was launched. And for the
5:49next 12 months, everyone, including me,
5:52waited for the results, thinking this
5:55might be it. This could be the
5:57breakthrough everybody has been waiting
5:59for. This could actually be the thing
6:01that takes somebody from nearly fully
6:03bald to fully haired. And then
6:07nothing, nothing, nothing at all. In
6:092024, that research group announced that
6:12the phase 2 clinical studies had been
6:14completed. And then the company never
6:16even bothered submitting the results of
6:19the report. And then in 2025, a press
6:22release was issued about the phase 1
6:23human study on HMI 115 on a whopping 16
6:27people. The findings, it appeared safe,
6:30but it only regrrew about 14 hairs per
6:32square centimeter. That's a far cry from
6:34the 100 plus hairs per square centimeter
6:37on average seen in that monkey study.
6:40And all of a sudden, enthusiasm
6:41surrounding HMI5 and even prolactin's
6:44role in hair loss all but collapsed.
6:47Well, all except for maybe one person,
6:50and that was Andreas Bush. He contended
6:53that the hypothesis on prolactin and
6:55hair loss still could be right, but that
6:58the monkey study did not translate to
7:00the humans not because of differences in
7:02hair loss pathology, but instead because
7:05he thought the humans were underdosed,
7:09that their prolactin wasn't adequately
7:11reduced in the way that it was for the
7:13monkeys, and that the pharmacocinetic
7:15data later released by Bay
7:17Pharmaceuticals, according to him,
7:19actually proved it. And this is where
7:21Andreas Bush's journey moves from Bear
7:23to another company, ABSI, and from HMI
7:271115 to a partnership with Absi's
7:30founder, Shawn Mlan, and his research
7:32team to develop a better drug, one that
7:36fixed the problem in the original study
7:38on HMI 115, and one that would finally
7:41put to rest the thesis about prolactin
7:43and whether it was actually at the root
7:45cause of hair loss. And this is where
7:48our conversation with Shawn Mlan begins.
7:51I'll present this interview in two
7:53stages. First, I'm going to get out of
7:55Shawn's way. He has a compelling case to
7:58make about prolactin's role in hair
7:59loss, ABS 2011, their ongoing clinical
8:02trials, and that steelman argument
8:05deserves to be presented uninterrupted.
8:08And only after that will I then show you
8:10my questions to Shawn and how that
8:12altered aspects of our discussion.
8:14Prolactin
8:16has
8:17maybe had a a bad rap and I think it was
8:20just due to uh the naming you know
8:23prolactin is you know prolactation
8:25everyone thinks of it as a uh lactation
8:28hormone or or in women's health but what
8:31you see is that u prolactin is expressed
8:35all throughout the the body both in
8:37females but as well as males. You you
8:40actually see it in in the scalp. You see
8:42it in the the your joints. Uh you you
8:45see it in in in your heart. Uh in your
8:48bones it and it and it plays a really
8:51interesting uh role.
8:52>> Sean is describing our evolving
8:55understanding of the hormone prolactin.
8:57Originally only seen as a female
8:59hormone. Researchers have now found that
9:01prolactin is actually all over the body
9:03in men and in women. And its role in
9:06human health is not just relegated to
9:08lactation. It looks like it sits on this
9:11uh stress inflammatory uh axis, you
9:15know, in diseases like indometriosis um
9:18or even androgenic alopeesia. It's
9:19driving uh you know, in inflammation.
9:22Essentially, we have new work that
9:24hasn't been published yet, but it looks
9:25like, you know, it does have a role in
9:27in in metabolism. I think we're just
9:29starting to realize how important um
9:32prolactin's uh role is in in both male
9:36and females and you know in in the role
9:39of you know androgenic alipcia,
9:41autoimmune diseases uh and uh and and
9:45just kind of immunology in general. So
9:47Shawn sees prolactin as a hormone that's
9:49often elevated in conditions linked to
9:52inflammation, endometriosis, potentially
9:54some metabolic disorders, even
9:56androgenic alopecia. And at this stage,
9:59it's important to understand how
10:01prolactin is even arriving to these
10:03sites in the first place. Well, first,
10:05prolactin is made by our pituitary
10:07gland. That's the p-sized organ that
10:09sits at the base of our brain. And that
10:11prolactin will enter our bloodstream and
10:13then travel through a highway network to
10:16other places in the body where it can
10:18then attach to other organ sites and
10:20begin to influence the behavior of those
10:23cells. But according to Shawn, that's
10:25not the only way that our bodies make
10:27prolactin. There's also prolactin that
10:29our own organs can manufacture on site.
10:32And it's this production of prolactin
10:34that varies wildly in individuals. And
10:37it means that two people can have the
10:39same exact levels of blood prolactin,
10:41but then if you actually look at their
10:43tissue levels, they can be wildly
10:46different. So you have the classical
10:48pituitary
10:49um expression of of prolactin. Uh but
10:52then you also additionally have and and
10:55a lot of people don't un or or know this
10:57is that prolactin sits on a uh an
11:01additional promoter that controls the
11:04extra pituitary
11:06um uh expression. And so you could have
11:09normal systemic levels of prolactin that
11:13come from the pituitary, but an
11:15increased level of prolactin uh within
11:18the scalp and and it's being driven off
11:21of that extra pituitary promoter. And
11:23what's really interesting is that the
11:26transcriptional uh uh factors that that
11:30drive the extra pituitary u expression
11:33are completely different than what you
11:35see in um in the pituitary. So they're
11:39completely uh independent and I think
11:41that that's why for a long time
11:45this hasn't come up as a um potential
11:48you know prolactin being a potential
11:50cause of of hair loss cuz we've been
11:53looking at at you know systemic blood
11:55levels uh versus looking at what is the
11:58the actual expression within the scalp
12:01and you can have really high expression
12:02in the scalp but have completely normal
12:05um prolactin levels. One of the things
12:06though that we don't really know is that
12:09how does systemic prolactin
12:12uh in addition contribute to what's
12:15being locally um produced as as well.
12:18That's one of the um you know factors
12:21that we we still don't quite understand.
12:23>> Okay. So we see elevated levels of
12:25prolactin in organs affected by
12:27inflammation and autoimmunity. But just
12:29because something is higher in a
12:30diseased organ, that does not mean that
12:32the thing that's elevated is causing
12:34that disease. For a perfect example of
12:36this, look at blood levels of C reactive
12:39protein or CRP. CRP is often elevated in
12:42people with actively evolving
12:44atherosclerosis.
12:45And so researchers once wondered if CRP
12:48was actually causing that
12:49atherosclerosis. But later research was
12:51able to tease out that this wasn't the
12:54case. That CRP was elevated as a
12:57reaction to other inflammatory
12:58processes. In other words, it wasn't a
13:01cause of the inflammation. It was an
13:02effect. it was a surrogate of the
13:04inflammation happening. So in that same
13:06vein, what exactly is the evidence that
13:08causally links prolactin to androgenetic
13:11alipcia? Because I have to be honest
13:13with you, at first glance, the idea of
13:15prolactin causing androgenetic alopecia
13:18sounds crazy because the name of the
13:20condition describes its causes.
13:23Androgens, male hormones like DHT, and
13:26genetic, your genes. And it's not like
13:28somebody just gave this condition this
13:30name and called it a day. These causes
13:33were established over 100 years of
13:35research. Men who can't produce the
13:37hormone DHT, they never go bald. When
13:40you expose balding, sensitive scalp skin
13:42to DHT, it damages the hair follicles.
13:45And when you lower DHT levels in balding
13:48men with drugs like finasteride or
13:50dutastasteride, 80 to 90% of them will
13:53see a slowing, stopping, or partial
13:55reversal of their hair loss with results
13:57sustaining for decades. So you have
14:00decades of observational, mechanistic,
14:03and interventional data that all
14:05converge on the hormone DHT causing this
14:08condition. So where on earth does
14:10prolactin fit into this? And
14:12interestingly, Shawn doesn't refute
14:14DHT's role in androgenetic alopecia. He
14:17thinks it's absolutely causal. He just
14:19argues that DHT doesn't just magically
14:22appear in balding scalps. It increases
14:25in part because of prolactin. And not
14:28only that, but by targeting prolactin,
14:31he thinks we might even be able to
14:33overcome some of the biggest hurdles
14:35that prevent people from getting huge
14:37hair recoveries even after they lower
14:39their DHT.
14:42The name is actually very misleading,
14:44androgenic alipcia. It implies that it's
14:47androgen driven. Yes, androgens are a
14:49part of it, but from what we're seeing,
14:52prolactin actually sits potentially
14:55upstream of the androgen receptor. And
14:58we actually even have data that that
15:00does show that um prolactin drives uh
15:03increase in androgen uh transcript and
15:07and so it does look like it regulates uh
15:10the androgen receptor. There's a lot to
15:12unpack here, but basically Shawn is
15:14suggesting that when prolactin arrives
15:16to a balding scalp, it activates
15:18androgen receptors, which are what cells
15:21use to allow hormones like DHT, to
15:24attach to those cells and then exert
15:25their effects. And if I were to brutally
15:28simplify the old guard versus new guard
15:31or new hypothetical argument for
15:33androgenic alipcia, the old argument
15:36looks like this. after you hit a certain
15:38age, your genetics will cause DHT levels
15:41to rise in the scalp, and those DHT
15:43levels will then cause pattern hair
15:45loss. What Sean is saying, it adds a a
15:48step right here and a step right here.
15:50So, it doesn't nullify decades worth of
15:52data. It just adds steps to what's
15:54happening and makes the chain of events
15:56a little more specific. So, that is the
15:58supposition.
15:59But what is the evidence to support that
16:02supposition? In our interview, Shawn
16:04builds his case starting with
16:06observational data on genes, prolactin,
16:09and severities of balding. What we did
16:11here was we we took a look at the uh UK
16:15bio bank and uh evaluated um how changes
16:22in prolactin uh expression or prolactin
16:26receptor expression uh changed the the
16:31uh the outcome of of balding. And and
16:34what we saw was was really really uh
16:37pretty uh uh remarkable was that in
16:41those that were not balding or had very
16:44little balding, they had much lower
16:47prolactin receptor uh levels. And those
16:51individuals
16:53that had, you know, moderate to severe
16:55balding, you saw uh an increase in the
16:59overall um prolactin receptor uh
17:03expression.
17:04>> So to reiterate, Sean's team took
17:06genetic data from over 165,000 men in a
17:10database and then he focused an analysis
17:12on genes that control for prolactin
17:14receptor expression in cells. Now, some
17:17genes will relate to more prolactin
17:19receptor expression, others less. And
17:22then his team compared those genes to
17:24the men's self-reported severities of
17:26hair loss. Zero being no hair loss, four
17:29being severe hair loss. And they found
17:31that men with little to no hair loss
17:33also happened to have genes linked to
17:35lower prolactin receptor expression. And
17:38men with lots of hair loss had genes
17:40linked to higher prolactin receptor
17:42expression, which they also plotted in
17:44this chart. The thing that's pretty
17:46remarkable about this is these are like
17:48very very small changes in prolactin
17:51receptor expression. Uh and by very
17:56small changes, you're still able to
17:58actually see an effect in in male
18:01pattern baldness. Uh you know, these
18:03aren't massive changes in in overall
18:05expression, just minor minor changes.
18:08But we know that association doesn't
18:09equal causation. Ice cream sales are
18:12linked to shark attacks, but ice cream
18:13sales do not cause shark attacks. The
18:16confounder is the warm weather getting
18:18people to buy ice cream, but also to go
18:20to the beach and also into the ocean. So
18:23observation by itself is not enough. And
18:26then we have to ask what else is there
18:28that might causally link prolactin to
18:31androgenic alopecia. Well, even before
18:33Absai and Bear thought to target
18:35prolactin for androgenic alopecia
18:37research, Shawn actually told me about a
18:39research paper from 2006 by Ralph Paws
18:42and it showed in biopsies of human hair
18:45follicles that hair follicles could make
18:47prolactin on site and that prolactin
18:50could also trigger those hairs to shed.
18:53So that's a little data, but more
18:55interesting is some of the mechanistic
18:57work that Shawn and his team later did
18:59to start to tease out cause and effect
19:01between prolactin and balding. Some of
19:04which has not yet been made public until
19:06this interview. What we did here was we
19:08actually took uh human uh scalp biopsies
19:12uh of both male and female and what I'm
19:15showing here is is male and we then um
19:19cultured it in uh with ABS 2011 uh which
19:23is uh our antiproactin receptor um
19:26blocking antibbody and uh additionally
19:30uh um cultured it with prolactin and
19:32then had a rescue arm where we added
19:34both prolactin as as well as uh ABS
19:382011. And uh what you see here is uh how
19:43much hair uh was grown uh in a 3-day um
19:47period. And this is, you know, the the
19:49same um type of measurement uh that is
19:52actually going to be done uh in uh the
19:55clinical study uh looking at um the
19:58photography and seeing how much uh hair
20:00was actually grown. And you can actually
20:01see here um within a 3-day time period,
20:05ABS uh 2011 was able to uh increase hair
20:09growth uh and you you you saw more hair
20:13follicles go into the uh antigen state
20:16and um prolactin um when you added it uh
20:20essentially shunted the overall growth.
20:23And by adding both prolactin and uh the
20:26the receptor uh uh or and and the
20:29antibbody, you're able to rescue uh the
20:32the follicle.
20:33>> So here Sean's team took scalp biopsies
20:35from three balding men. And then they
20:37exposed their skin to either nothing at
20:39all or their prolactin receptor
20:41antibbody drug ABS 2011 or more
20:44prolactin or more prolactin plus ABS
20:482011. 3 days later, the samples exposed
20:51to ABS 2011, they grew longer hair and
20:54they still had more of their hairs in
20:55the growth phase of their hair cycle
20:57than the samples that were left
20:58untouched or given more prolactin. The
21:01implication from this Xvivbo research is
21:03that blocking prolactin might improve
21:05hair parameters in scalpkin samples of
21:07androgenic alopecia. Now, this is great
21:09and all, but growing longer hair or
21:11having hairs shed less frequently does
21:13not explain what happened in these
21:15stumptailed macaks. These monkeys saw
21:18near full hair regeneration and near
21:20full hair repigmentation.
21:23This is a level of recovery that simply
21:26does not happen in humans with
21:27androgenic alopecia. It also is very
21:29rare to see in other monkey studies as
21:31well. In fact, in humans in specific,
21:34studies show that if you take your DHT
21:36as low as you can or you stimulate hair
21:38growth with drugs like minoxidil, on
21:41average, the best that you can expect is
21:43that you'll be able to rewind the clock
21:45on how your hair looks by around 6
21:47months to 36 months. That's an average.
21:50Some people do a little bit better, some
21:51people do a little worse, but after that
21:54point, it's like people hit a wall. You
21:57just don't get more hair back. And the
22:00question is why? And at least so far,
22:02researchers have identified three
22:04possible reasons. First, when you have
22:07advanced stages of hair loss, hair
22:09follicles will develop scarring or
22:10paraphilicular fibrosis. And this might
22:12act like scaffolding that inevitably
22:14blocks hairs from shedding out and then
22:17resizing as thicker. So, in this case,
22:19you can reduce the DHT all you want. You
22:21can stimulate the hair to grow all you
22:22want. But if you don't get rid of that
22:24scaffolding, you're not going to be able
22:25to allow for the hairs to resize as
22:27larger in subsequent hair cycles.
22:29Second, after hairs become miniaturized
22:31beyond a certain point, research
22:34suggests that they become detached from
22:36their goosebump muscle. That's the
22:37erector pilli muscle. And research so
22:39far seems to show that while we can save
22:42hairs that haven't yet detached from
22:43that muscle, we've not yet reliably seen
22:47evidence that any treatment available
22:49today can reattach hairs that have
22:51detached from their erector pilli. So
22:53hairs that are miniaturized beyond a
22:55certain point just don't seem to be able
22:57to be saved. And again, reduce all the
22:59DHT you want, growth stimulate all you
23:02want. If you can't get that attachment
23:04back, you're not going to recover those
23:05hairs. And the third possibility is that
23:08at some point in the balding process,
23:11hair follicle stem cells which tend to
23:13be preserved even in advanced stages of
23:15hair loss, they start to lose their
23:17ability to convert from stem cells to
23:20other cell types like progenitor cells.
23:22And this failure step is why current
23:24treatments might not yet be able to
23:26fully revive those miniaturaturized
23:27hairs. And so for a prolactin receptor
23:30antibbody to do something like this in
23:33humans that's not coming from hair
23:36elongation. It's not coming from a
23:38longer growth stage of your hair cycle.
23:40That's quite literally hair
23:41regeneration. It's taking a fully
23:43vevelis hair and returning it to a fully
23:45terminal hair in many cases. It's
23:46solving somehow one of these rate
23:49limiting regrowth factors that we know
23:51about in androgenic alopecia. And so I
23:53asked Shawn about this and if his team
23:54had thought about this and it turns out
23:56they had. And not only had they thought
23:58about it, but they had run an experiment
24:01and they think they might actually have
24:02identified which of these rate limiting
24:04recovery factors their treatment could
24:06address. It's the stem cell failure.
24:09>> One of the big things that that you see
24:11uh with uh balding individuals is that
24:15they lose their progenitor uh uh cells
24:18over time. Um and as you slowly lose
24:21those over time, you get more and more
24:23uh miniaturization
24:25uh that that occurs. some of the data
24:27that that we generated um where we were
24:30able to see that uh ABS um 2011 uh is
24:35able to uh actually increase um the the
24:39proliferation of the K15 uh stem cell um
24:43population uh and it prevents the
24:46apoptosis
24:48uh which is is really great to to see.
24:51You see prolactin on on on the right
24:52hand side uh does drive um apoptosis of
24:56the uh K15 uh stem cell. And what's also
25:02uh really quite interesting
25:05is uh the progenitor uh cell line. What
25:10we see is the uh CD34 cells um are are
25:16decreased um when you add prolactin uh
25:20to these uh Xvivo u uh models. Again,
25:24these are human um um scalp biopsies.
25:27And so we do believe that blocking
25:31prolactin receptor uh is is able to at
25:34least um um uh keep the K15 stem cell
25:38population where it is and and be able
25:40to stop uh the uh CD34
25:44uh stem cell population from further uh
25:46uh depleting. So we we do think that
25:49there is this this ability to actually
25:51have a regenerative uh effect here.
25:54Currently there is no therapy that is
25:58able to reverse that that that stem cell
26:02niche and you know potentially be able
26:04to reverse uh the the
26:05miniaturaturization
26:07and this is where we think ABS 2011 uh
26:10could have a a big role here. Sean is
26:13saying that this mechanistic data
26:15suggests that if we block prolactin with
26:17ABS 2011, we might also be able to stop
26:20hair follicle stem cell degradation,
26:22improve their differentiation into other
26:24cell types, and that we might be able to
26:27overcome this rate limiting regrowth
26:28factor that other hair loss medications
26:30that exist today have failed to address.
26:33And that's how we might be able to
26:34explain these monkey results. But he
26:37also went a step further and he shared
26:38data not yet released in any public
26:40setting that he feels further
26:42corroborates this hypothesis.
26:44>> One of the phenotypes that has been
26:47shown is that uh collagen 17A uh
26:51decreases over time with the the stem
26:54cell uh population. And collagen 17A is
26:59really important uh in the sense that
27:01that is what anchors the stem cell
27:04population uh to the to the actual hair
27:07follicle itself. And what you see is
27:09that this gets degraded uh over time.
27:12And so the fact that you're actually
27:15modulating the stem cells in addition to
27:19increasing collagen 17A when blocking
27:22the the prolactin receptor uh is is
27:26really quite encouraging and and showing
27:28that indeed prolactin may sit up you
27:32know uh you know you know pretty far
27:36upstream where you know prolactin is is
27:38driving the the degragation of the stem
27:40cell niche. it, you know, it uh, you
27:43know, drives uh, it doesn't replenish
27:45the collagen 17A and then it's it's
27:48driving the the inflammation that that
27:50you see as as well. And so, uh, we we
27:52are encouraged to uh, see again this is
27:57a a 6 day uh, culture. So, you you have
28:01to kind of take it for what it is, but
28:03it is a human biopsy. And the the fact
28:05that we are seeing results in 6 days is
28:10is really incredible. The fact that
28:11you're actually regrowing the the hair,
28:13showing what prolactin does, you know,
28:16showing uh how prolactin uh is driving
28:19some of the same phenotypes that that we
28:21see uh in in prior research is is is
28:24really quite exciting. And so you're
28:26you're hitting on kind of a a whole
28:29different mechanism that both minoxidil
28:32as well as uh the you know androgen
28:35receptor uh um u you know mechanisms are
28:38are unable to uh to to to ultimately
28:42address.
28:43>> So there it is. That's the hypothesis
28:45around prolactin and androgenic
28:47alopecia. In balding hair follicle sites
28:49prolactin begins to increase. This
28:52causes a whole cascade of events. In one
28:55cascade, prolactin might increase
28:57androgen receptor expression, which then
28:59increases DHT, which then damages the
29:01hair follicles, causing them to shed
29:03prematurely and then come back
29:05miniaturaturized in the next hair cycle.
29:08And simultaneously, in another cascade,
29:10prolactin may degrade collagen 17A,
29:13which anchors the hair follicle stem
29:15cell bulge to the hair follicle itself.
29:18And with enough degradation, this then
29:20prevents the conversion from hair
29:21follicle stem cells into progenitor
29:23cells, which then limits our ability to
29:25regenerate hair that's already fully
29:27miniaturaturized, especially with DHT
29:29reducing treatments like finasteride or
29:31dutastasteride or even some treatments
29:33for females that are more powerful
29:34androgen receptor antagonists like
29:36spironolactone, flutamide, and
29:38bicolutamide because these things they
29:40only target part of the equation that
29:42Shawn proposes. But by blocking
29:44prolactin from reaching the hair
29:46follicle at all with a prolactin
29:48receptor antibbody like ABS201,
29:51Shawn argues that both of these
29:54disregulation cascades might get
29:56addressed and that because we're
29:58addressing both simultaneously rather
30:00than just one and we're targeting
30:02something further upstream than just
30:04DHT, these crazy monkey regrowth results
30:07all of a sudden might become a reality
30:10for people. And with this model, the
30:12monkeykey's continued hair regrowth even
30:13after quitting treatment becomes at
30:15least partly explainable because once
30:18those stem cell bulge connections are
30:20reestablished, hairs might just keep
30:22getting thicker and thicker in
30:24subsequent hair cycles regardless of
30:26whether you're continuing that treatment
30:28because it also takes time to build them
30:30and it takes time to degrade them as
30:32well. So, it's an enticing hypothesis,
30:35but then if the hypothesis is even true,
30:38why did HMI 115 fail to regrow hair
30:40appreciably in humans? I mean, it barely
30:43got any regrowth. Well, this is where
30:46Andreas Bush, the man who ran the
30:48original HMI 115 studies in monkeys,
30:51teams up with Shawn and proposes a
30:53datadriven conviction. The hypothesis on
30:56HMI 115 and prolactin was not wrong. the
31:00humans in the study were simply
31:02underdosed. And it's this very premise
31:05that led Andreas Bush, Sha, and Absai to
31:08develop a new drug and rerun this hair
31:11loss experiment in humans in what's
31:13currently a phase 2 clinical trial going
31:16on right now. Now, here's what Shawn had
31:18to say about the differences between HMI
31:21115 and ABS 2011. There are a lot of
31:24technical terms here. I will stop and
31:26explain them as we go, but this is the
31:29core thesis behind what Sean's company
31:31hopes will become a billiondoll drug.
31:34>> What you saw in the stumptails was 90%
31:38receptor occupancy and
31:42what you saw from the HMI115 data from
31:46the P. So they they publicly released
31:47the PK data and then we modeled the RO
31:51based off of of that. And it's it's
31:54really quite quite uh uh shocking and uh
31:57I think you'll you you'll see why we're
32:00quite confident in the profile that we
32:03have.
32:04>> Okay, so what is Shawn talking about?
32:0690% receptor occupancy PK data. What
32:09does all this mean? Well, first Shawn is
32:11referring to what he describes as
32:13publicly released pharmacocinetic data
32:15on HMI 115. PK stands for
32:18pharmacocinetics. That's basically just
32:20the study of how a drug behaves in your
32:23body, where it goes, how long it stays
32:25there, that kind of stuff. And what Sean
32:27is saying is that in this study on
32:29monkeys, HMI 115 was able to block 90%
32:34of those monkeys prolactin receptors. In
32:36other words, HMI15 achieved 90% receptor
32:40occupancy. And this is important because
32:42the more prolactin receptors occupied by
32:45HMI 1115, the less that prolactin can
32:48then attach to that cell and the less
32:50that prolactin can then affect it. So
32:53the more that you block, the less
32:55prolactin will have as an influencer on
32:58that cell's behavior. And at least in
32:59this monkey study, when you hit 90%
33:02receptor occupancy for prolactin, it
33:05seems to be doing some really impressive
33:07things. But this is the critical point
33:09that Sean is about to make.
33:11>> What's really interesting about the
33:14prolactin receptor is that you have to
33:18block it pretty substantially
33:21in order to completely block it. What do
33:26I mean by this? even if you're at let's
33:28say 60 uh 70 even you know 80% um
33:33receptor occupancy you could still have
33:36full activity of the the actual um
33:40pathway until uh you block it um you
33:43know substantially.
33:44>> Now what Sean is talking about here is a
33:46concept known as receptor reserves or
33:48spare receptors. Basically, this is a
33:51biological phenomenon where for certain
33:53hormones, your cells will express a ton
33:56of receptors to capture them such that a
33:59majority of those receptors that are
34:00active probably aren't even needed.
34:02They're considered spares. One of the
34:05most dramatic examples of this is with
34:07the hormone insulin. In muscle cells,
34:10you can have 100 insulin receptors
34:12available. And yet, insulin only needs
34:15to attach to one of them to exert its
34:17maximal metabolic effects on that muscle
34:20cell. In other words, it doesn't matter
34:22if insulin attaches to just one receptor
34:25or 99 of the receptors. The cell's
34:28behavior does not change after one. So,
34:30if you wanted to create an insulin
34:32receptor blocker that was effective,
34:35you'd literally need to find one that
34:37blocked as close to 100% of insulin
34:39receptors as possible. Because if the
34:41blocker only blocks 99% of them, that
34:44medication has zero effect. And it turns
34:47out this same receptor reserve
34:49relationship may also exist with
34:51prolactin. For instance, in one study on
34:54lymphoma, prolactin hit its maximal
34:57effect on cell growth at just 35%
35:00receptor occupancy. So you could be at
35:0235% or 100% and the same growth
35:06trajectory occurred. And what this means
35:07is that if you made a prolactin receptor
35:09blocker that blocked a whopping 65% of
35:12prolactin receptors, well, in this
35:14lymphoma study, your prolactin receptor
35:17blocker would still be 100% useless. In
35:20fact, in that study, even if you blocked
35:22prolactin receptors by 80%. You'd still
35:25see prolactin exerting more than 90% of
35:27its maximal growth effect on those
35:30cells. So, think of it like failing a
35:32test. It doesn't matter if you got a 59
35:34out of 100 or a one out of 100, you're
35:37still getting an F. And so now the
35:39question becomes with HMI 115 these
35:42monkeys were suspected to hit 90%
35:46receptor occupancy RO but did the same
35:50actually happen in the human clinical
35:52trials according to Sha and Andreas Bush
35:55the answer is no. What you see from HMI5
36:00data here again this was they publicly
36:04disclosed what the PK profile was in
36:06their phase one. We then modeled out
36:08what the RORO um would be based off of
36:10the the publicly available data. And you
36:14you see that uh it takes quite a bit of
36:17time uh for the HMI115 molecule uh to
36:22actually uh ramp up to um you know
36:26roughly 70% uh receptor occupancy is is
36:29the the CAX or 72 73 and it then
36:34oscillates. Now what's the significance
36:37of the oscillation? So when you block
36:41prolactin receptor, you actually get an
36:43increase in prolactin levels. And if you
36:47then dip below a certain receptor
36:49occupancy threshold, you could actually
36:52be activating the the prolactin receptor
36:55with the increased levels of prolactin
36:58that are in the system. So you're
37:00inadvertently going in between antigen
37:04and kadagen. antigen, kadagen, antigen,
37:06kadagen. And we know that it takes time
37:10to rebuild the stem cell niche. And you
37:13need a sustained
37:15uh level of receptor occupancy for a
37:18long period of time uh to be able to
37:21rebuild that stem cell niche. And we
37:25believe this is the reason why uh HMI115
37:29did not uh achieve the the full efficacy
37:32because they they weren't able to give
37:35the hair follicle kind of a long enough
37:38time to uh actually rebuild that stem
37:40cell niche um because it was kind of
37:42constantly oscillating in and out of
37:45antigen and and kadagen um phase versus
37:48you know what you see with with our
37:50molecule is that you get uh sustained
37:53the levels of greater than 90% receptor
37:56occupancy for for 6 months uh straight.
38:00Uh and and and we're above the 90%
38:03receptor occupancy which again is what
38:05you saw in in the stumptail macak and
38:09again
38:10we believe in the mechanism based on
38:12everything we've we've told you. It just
38:15came down to a PK and dosing issue with
38:19HMI115. So now you have the core thesis
38:21behind ABS 2011. Andreas, Shawn, the
38:24broader ABSI team, they developed this
38:27drug to solve for this receptor
38:28occupancy problem. And their phase 1 and
38:31pharmacocinetic studies according to Sha
38:33prove that ABS 2011 achieves a prolactin
38:37receptor occupancy level of greater than
38:4090%. That's a lot. And being above that
38:4290% receptor occupancy threshold
38:45according to Shawn through inferences in
38:46this monkey data is the level that you
38:48need to adequately suppress prolactin
38:50levels in hair follicles which with
38:53sustained suppression will hopefully
38:55give the stem cell bulge enough time to
38:57rebuild which is what we need to achieve
39:00truly regenerative effects in humans.
39:02And it's this very premise that guided
39:05Shaun's team through pre-clinical work,
39:08then phase one human studies for safety,
39:10and now a phase 2 human study on men and
39:14women with androgenic alopecia. And
39:16this, Shawn believes is the test that we
39:19need to truly ascertain if this
39:21hypothesis surrounding prolactin and
39:23hair holds validity and if this
39:26treatment target might be the
39:28breakthrough the entire hair loss
39:30community has been waiting for. This
39:32phase 2 study, it is already underway
39:34and in December of this year, Shawn and
39:36his team plan to do a preliminary
39:3913-week read and an announcement of the
39:42data.
39:42>> The 13we data readout that's going to
39:45come in December. We have not given firm
39:48metrics on what we would like to achieve
39:51there. We have talked about it being
39:53directional. We want to see that the
39:55mechanism is is is working and that
39:57there is kind of a path to uh 30 plus
40:01hairs per square centimeter at at 26
40:03week. And so I think that we have set
40:06ourselves up in a way that again this is
40:09a more an exploratory look at how the
40:13mechanism is is performing uh to to
40:16date. Uh, additionally,
40:19we do feel good about the readout at at
40:2326 weeks, but
40:25let's say we achieve 30 plus at at 26
40:29weeks. My guess is that 9 12 months, you
40:34continue to see an increase uh from from
40:37there. Um, but you know, we are
40:39confident that
40:42you'll see, I think, strong or good
40:46results at at at 26 weeks, but that
40:48doesn't take away from the fact that you
40:50could continue to see uh hair regrowth
40:53past uh 6 months. And and the great part
40:56about that is we are actually going to
40:58be tracking these patients for a year
41:01post uh treatment. So we are going to
41:03understand like how
41:05the you know uh how how the changes are
41:08are progressing over over that year um
41:10post treatment. So I think that that'll
41:13also be a really exciting uh insight
41:15that we're going to see as well.
41:16>> And here's the part that I really
41:18appreciated about my conversation with
41:19Shawn. So I voiced to him about how
41:22frustrated I've been this year and last
41:24year with all of the press releases from
41:25other companies that are pursuing future
41:27hair loss treatments. The through line
41:30here is that there is a massive amount
41:32of data withholding, manipulation of
41:34statistics, disingenuous comparisons
41:35across hair count groups, subgroup of
41:38subgroup analyses, the absence of
41:40reporting and critical metrics like
41:41absolute terminal hair count changes.
41:43And so I just asked him directly that
41:44regardless of these 13week results if it
41:47would be possible if he could commit to
41:49just not pulling any of these weird
41:51statistical stunts or obscurities in the
41:54way that data is reported. And here is
41:55what he said. I can promise you that we
41:58will have a non-controversial
42:01data cut. We are not going to do a sub
42:03population of sub population like it.
42:05It's going to be clear-cut
42:08uh data that will be uh easy to to
42:12interpret.
42:12>> And that to me is amazing news. So kudos
42:15to Shawn for this. And in December or
42:17January, you can bet that I'll be making
42:19a follow-up video about that press
42:21release and the data. I hope that it is
42:23fantastic.
42:25So this about wraps the Steelman case
42:27for prolactin, its role or potential
42:30role in androgenic alopecia, HMI 115,
42:33why it supposedly failed, the evolution
42:35to ABS 2011, and how lowering prolactin
42:38might unlock near full levels of hair
42:40regrowth. And I really want to present
42:42Shawn and the broader data here in the
42:44strongest way possible. I wanted to slow
42:47down the storytelling to reiterate
42:49information that was key to add support
42:50where I could because he reached out to
42:53us. He gave me a ton of time. We had two
42:55calls. The first one was an hour. The
42:57second one was 2 hours. He's committed
42:59to giving public and uncontroversial
43:01reads of ABS 2011's 13week data. And
43:04that part of the discussion here
43:06deserves to stand alone without my
43:08interruptions, without my nitpicking,
43:10because it truly is a service that Shawn
43:12took the time to do this. But I
43:14obviously asked Shawn a ton of questions
43:15during our conversations because I
43:17wanted to improve my clarity on the
43:19strengths, but also the limitations of
43:21the evidence presented. And in this
43:23respect, I always think that we should
43:24remain hopeful about future treatments
43:26and the work going into them. But in
43:28general, it usually helps to have a
43:31precaution to temper expectations about
43:34what a clinical trial is going to do.
43:36Because as it stands, I think the data
43:39around prolactin and hair loss is
43:41compelling in some respects and limited
43:44and potentially conflicting in others.
43:46And I'll get into that level by level
43:48right now.
43:50First, let's start off with HMI15's
43:53monkey data. The results are absolutely
43:56incredible. I mean it when I say that
43:58I've never seen monkey results to this
44:00degree and the continued hair regrowth
44:02post treatment withdrawal, I have never
44:04seen that in any androgenic alopecia
44:06study, monkey or human before. But is
44:08this magnitude of regrowth truly
44:10unrivaled in monkey studies? Not
44:12necessarily. While it's not the same
44:14recovery, take a look at this study on
44:16stumptailed mac and minoxidil. In
44:19humans, topical minoxidil tends to
44:20produce relatively modest hair gains.
44:23The cosmetic results tend to peak around
44:24six to eight months and then you plateau
44:27and even slowly decline thereafter. But
44:29in this monkey study, the monkeys using
44:32minoxidil, they just kept regrowing
44:34hair. They regrrew hair at month three,
44:36at month six, and at month nine. In
44:38fact, they kept regrowing more and more
44:40hair all the way up until they withdrew
44:41from treatment. So these monkey models
44:44can directionally translate to humans
44:47with androgenic alopecia, but they're
44:49not perfect surrogates by any means. In
44:51fact, in my opinion, I think that
44:53reconverting vellis hairs into terminal
44:56hairs in monkeys is just a ton easier
44:58than it is in humans because the
44:59treatments that seem to do it in monkeys
45:01like minoxidil, when you apply those to
45:03humans, you don't get the same results.
45:07You get the same direction in results.
45:09You don't get the same magnitude of
45:11results. And it's not just minoxidil.
45:14We've also seen the magnitude of results
45:16really decrease with other treatments
45:18when Latanoprost or Bataprost moved from
45:21monkey models to humans. They went from
45:24pretty impressive results to very tiny,
45:27ambiguous, and cosmetically
45:29insignificant results. So again, we have
45:32to temper our expectations. What we see
45:34in these monkeys directionally might fit
45:36with humans, but the magnitude of
45:38impact, it might be very tiny. We don't
45:40know yet.
45:42Next, let's talk about this genetic data
45:44that Shawn presented. Now, Shawn showed
45:45us some charts suggesting that genes
45:47linked to higher prolactin receptor
45:49expression were also linked to higher
45:51severities of balding. And Shawn noted
45:53in the interview that all it took were
45:55just tiny differences in prolactin
45:57receptor expression to show this
46:00relationship in the severities of
46:01balding. However, this observational
46:04relationship to me appears somewhat at
46:06odds with the idea that prolactin is a
46:09hormone with high spare receptors or
46:11receptor reserves. So, for instance, if
46:15this gene for prolactin receptor
46:17expression is linked to little to no
46:18hair loss, but this gene is linked to a
46:21ton of hair loss, and yet the difference
46:23in prolactin receptor expression across
46:25the genes is maybe 10, 20, 30, 50, 70%,
46:29even if it's 80%.
46:31Then what difference does that make if
46:33all prolactin needs to do to trigger
46:35hair loss is occupy 10% of those
46:39available prolactin receptors? With such
46:41a low threshold for prolactin to
46:42potentially have these adverse hair
46:44effects, wouldn't that imply that micro
46:47differences in prolacter receptor
46:48expression shouldn't matter at all that
46:50instead we would want to see 10 or
46:5220fold differences in expression
46:55activity before we start to see these
46:56problems? And yet, we can't really
46:59answer these questions right now because
47:01the data is so preliminary, but it's
47:03also really limited.
47:05Next, let's talk about some of the Xvivo
47:07data that Shawn presented. These studies
47:09on balding hair follicles are great
47:12mechanistic tools for research. But the
47:15one relationship that they don't
47:16establish is if all these same
47:19directional relationships with hair also
47:22exist in nonbalding scalp hair. Because
47:25if prolactin also does all the same
47:27exact things at the same exact
47:29magnitude, it stops hair elongation. It
47:32turns hairs from growing into resting.
47:35If it does that the same in balding hair
47:37samples as it does in non-balding hair
47:40samples, then this would actually weaken
47:42the case for prolactin causing
47:44androgenic alopecia. So I asked Sean
47:46about this in the interview and if they
47:47had done experiments with non-balding
47:49human scalp hair as well. And here was
47:51his response really quickly. So we can
47:54see that there's some degree of
47:56significance with those effect sizes on
47:58the slides you just showed. Those are
48:00from three male scalp biopsies with
48:03androgenic alipcia. Do you have control
48:06data on a scalp unaffected by androgenic
48:08alipcia as a comparator of any type?
48:11>> Uh we do not. We took it from an
48:13androgen sensitive uh area uh which is
48:17the frontal temporal uh uh region. Um
48:21but we did not have a uh healthy or a um
48:28non uh um you know balding sensitive uh
48:33uh area. Um so so we currently do not
48:36have that at the moment.
48:38>> Okay. Yeah. I'd be really curious to see
48:40if you see the same exact drops in an
48:43unaffected AGA scalp skin sample as well
48:46because then that would help to tease
48:47out whether or not those drops are truly
48:49relevant to the mechanisms being
48:51explored.
48:52>> Yeah, absolutely. And uh one of the
48:55things that I think we'll we'll we'll
48:57see uh actually before we even get data
48:59like that is actually how this performs
49:01in in in humans later this year.
49:03>> Now, for what it's worth, Sean's reply
49:05here is fair. You could spend your whole
49:08life running XVivo studies trying to
49:10guess what happens in a human.
49:11Eventually, you just need to prove
49:13safety as best as you possibly can and
49:15move on to human testing. But without
49:17those non-balding control samples, I
49:20personally don't find this mechanistic
49:22data nearly as compelling. And the same
49:24criticisms apply to research presented
49:26about collagen 17A. It's a fascinating
49:29hypothesis. New research indicates this
49:31could be a critical piece to the balding
49:33process and a rate limiting recovery
49:35factor with respect to androgenic
49:37alipcia treatment success. But without
49:39knowing how non-balding hairs also react
49:42and also express collagen 17a, we can't
49:46actually distinguish if any increased
49:48expression or decreased expression of
49:50anything is meaningful and if it's truly
49:54unique just to balding affected skin.
49:56And this matters even more when we
49:58actually revisit that original 2006
50:00paper from Ralph Poss. And we actually
50:02see that in that study, the effects of
50:05prolactin on human hair follicles, they
50:08were coming from nonbalding hair
50:10follicles. And yet the researchers found
50:12the same relationships.
50:14This study used occipital regions of the
50:17scalp during facelifts and hair
50:19transplant surgeries. And in both cases,
50:21those should be hairs that are
50:22relatively protected from the balding
50:24process that aren't as prone to DHT's
50:27mediating effects on androgenic
50:28alopecia. And yet, in that 2006 study,
50:31the same relationship seemed to exist
50:33with a non-balding human hair follicle
50:35as we're now seeing in the balding human
50:37hair follicle research 20 years later.
50:41Next, there's the discussion about
50:43safety, about lowering prolactin levels
50:46in cells and whether or not that's
50:48something that's safe long term. In
50:50women, hypoprololactinemmia is
50:52associated with an inability to lactate
50:54and it's also associated with
50:55infertility. Now, on their own website,
50:57ABSI sites papers to suggest that
51:01reducing prolactin is potentially very
51:04safe for many adverse events, but they
51:06mainly focus on safety metrics that are
51:08not fertility and not lactation. And
51:11because of this, I wanted to understand
51:12not only which adverse events of
51:14interest Shaun's team will be tracking
51:16in their clinical study. I also wanted
51:19to know how they were tracking the
51:21adverse events themselves. And there's a
51:23very specific reason why I wanted to ask
51:25this. I will show you the clip here. So,
51:27you mentioned Ferodmics just a second
51:29ago. I've been tracking their data as
51:31well. I think that anybody innovating
51:33and attempting to run well-designed
51:36studies in the hair loss space for
51:38interventions is incredible. So, I
51:41really appreciate what they're trying to
51:42do. When I looked at their clinical data
51:46and specifically their adverse events, I
51:48saw some things that didn't make total
51:50sense to me. So, we know that their
51:52formulation is uh a larger dose of
51:56minoxidil that is supposed to slow leak
51:58into your system over time. [snorts] And
52:00when we look at all of the clinical
52:02studies on oral minoxidil ranging from
52:040.25 25 milligrams and higher 60 to 90%
52:09of participants both male and female
52:11across literally all of the studies
52:13report hypertriosis.
52:15And when I looked at veroddermic safety
52:17data I saw the hypertriosis numbers at
52:19something like 3 to 6% which was
52:22comparable to the placebo group. So this
52:25means that either they have
52:26inadvertently developed a hypertargeted
52:29oral minoxidil that then attaches only
52:32to the scalp and does not affect hair
52:33anywhere else on the body which is not
52:35listed in any of their patents or there
52:39is something with their data collection
52:40with respect to safety that is not
52:43adequately capturing the real risk of
52:45hypertriosis that we would expect for
52:46this medication. Which then leads me to
52:49the question about how your team in your
52:51phase 2 clinical studies is capturing
52:53clinical adverse events reporting. Are
52:56these done through interviews with the
52:59investigators? Are these done through
53:01survey systems? Are they done through
53:04open-ended questionnaires? Each of these
53:06has their pros and their cons, and
53:08there's plenty of debate as to which is
53:10the best in clinical research and
53:12reporting. But I'm curious just to get
53:13your perspective on how you are tracking
53:15these things because earlier we were
53:17talking about libido and the potential
53:20for no effect, maybe even benefit from
53:23this type of therapy, but then libido is
53:27separate from semen parameters and you
53:29can have a strong libido and be
53:30completely infertile. And so I'm just
53:32kind of curious at this point for how
53:34you guys in your phase 2 clinical
53:36research have prespecified how you'll
53:38collect adverse events and the specific
53:40adverse events that you are exploring.
53:43>> Yeah, it's a great question. So first
53:45off, we have a fantastic chief medical
53:50officer. Uh he was the the SVP and head
53:54of clinical development at Vertex. uh
53:57prior to that he was at uh uh Amgen and
54:00you know has you know 20 plus years of
54:03uh very hardcore clinical development uh
54:06experience uh you know well outside of
54:09even you know dermatology. I mean he's
54:11he's run some of the most complex and
54:12and hard clinical trials. He actually
54:14ran a you know the Draavx the the NAV uh
54:181.8 8 uh clinical study which is a pain
54:21study and pain studies are notoriously
54:24very very challenging and and was uh
54:26successful in in in that study and so he
54:29has brought a lot of rigor into uh ABSI
54:34on the clinical development uh side and
54:37we are wanting to make sure that uh we
54:40have a uh robust uh study uh and you
54:44know we believe with how we have set up
54:47this study uh If successful, we see this
54:49as a um potentially a a dose range
54:52finding study where we can go on to a
54:56phase three clinical study. and and in
54:58terms of like the overall clinical
55:00operations, the the protocols that that
55:02we have in in place, uh I can say that
55:05they're of the the highest uh standard
55:07and uh you know, these um you know, the
55:11questionnaires and and how they're
55:12asked, they're they're all done uh in a
55:15way to uh really help uh uh do it in an
55:18unbiased uh uh way. And and we have a
55:21really incredible clinical development
55:23team on all the specific, you know,
55:25details. uh we'd have to bring him on to
55:28to kind of go through all of those. Um
55:29but uh I I I do know though that uh it
55:33is a is a very rigorous uh study and you
55:36know you can even look at how we
55:38designed the the phase 2 um clinical
55:40study. It's a you know it's a 3:1 um um
55:44um um placebo um uh uh controlled um
55:48double blinded uh study. Uh and yeah,
55:52really excited about the the overall um
55:55uh kind of results both on the efficacy
55:58as well as um being able to ensure that
56:00the uh you know adverse um uh events are
56:03are are um recorded and and uh uh done
56:06in an appropriate manner.
56:07>> By the way, I'll link our video on
56:09vermics below if you caught that
56:11comment. But in any case, Shawn
56:13preferred in this case to defer
56:14answering this to his head of clinical
56:16development. Also, it is totally fine to
56:19do that. He's the CEO of ABSI. He's not
56:22in the weeds leading every aspect of the
56:25clinical research projects, but adverse
56:27event tracking and how it's reported is
56:29one piece of a clinical trial protocol
56:31that basically almost never gets
56:33published publicly in a repository, but
56:36that is super important to understand
56:38because the way that you collect results
56:40can drastically change the outcomes. And
56:42those differences in results don't
56:44actually reflect product safety
56:45differences. they just reflect
56:47differences in the way that data was
56:48collected and that's the issue. So
56:50perhaps in the future we can get a
56:51little bit better clarity on this and
56:53it'll be one of the things that I'd love
56:55to focus on if and when it's time to see
56:57ABS size clinical data or if we're able
56:59to connect with their head of clinical
57:01research.
57:03Next, for veterans of the hair loss
57:05community, you will know that we have
57:07reached this milestone in research for
57:10hair loss treatments many times before,
57:12where observational, mechanistic, and
57:15even early interventional data all point
57:17toward a new novel breakthrough just
57:20around the corner for androgenic alipcia
57:22only for the human clinical trial to
57:24fail miserably. One recent example,
57:26prostaglandon D2 antagonism,
57:30specifically the drug setup.
57:32Observational data found that
57:34prostaglandin D2 was elevated in balding
57:36scalps. Mechanistic data suggested PGD2
57:39stopped hair lengthening. Monkey data on
57:41prostaglandin analoges like
57:43latannoprostatrost
57:45even to a certain extent minoxidil all
57:48showed impressive hair gains. And yet
57:50when a prostaglandon D2 inhibitor
57:52setipin was finally tested in men with
57:55androgenic alopecia
57:57there was literally no effect at all. So
57:59remain hopeful, but don't forget about
58:02the graveyard of prior prospective
58:05treatments that made it all the way to
58:07this point only to still fail a clinical
58:10trial. Statistically, it is the phase 2
58:13human study that tends to make or break
58:16most real contenders in the hair loss
58:18treatment space. And lastly, this one I
58:22really love. Even if ABS 2011 fails, it
58:26still actually does not disprove the
58:28hypothesis that prolactin might be a
58:30root cause of androgenic alopecia. It
58:32might turn out that it's still just not
58:34powerful enough of a prolactin receptor
58:37antibbody. Keep in mind that that
58:39lymphoma study I talked about earlier,
58:41even when prolactin occupied just 7% of
58:44the available receptors, cell growth was
58:47still at 50% its maximum speed. In this
58:50respect, we might actually find that a
58:52failed clinical trial on ABS 2011 simply
58:54means that we have to build something
58:55that suppresses prolactin even harder.
58:58It's wild to think about that fact that
59:00even with ABS 2011, a drug that was
59:02designed to overcome this one liability,
59:05we still might not be able to confirm or
59:07rule out the legitimacy of the
59:08hypothesis. And that is just the way
59:11that hair loss research goes.
59:14Okay, that is everything. I know this
59:16video was a long one. I hope that you
59:18enjoyed it. I hope that you learned
59:19something. We put a ton of time into
59:21creating it and I really wanted to thank
59:23Sean for taking the time to reach out
59:26and do this interview with us. I loved
59:28our discussion. I really appreciated his
59:30time and most importantly, I want his
59:32product to succeed. I think that if it
59:34does, it's going to be an incredible
59:36compliment or even a replacement to
59:39every other treatment out there. We can
59:41only hope and time will only tell. We'll
59:44know more at that 13week data read.
59:46However, even if the results are very
59:48tiny at 13 weeks, recall that the
59:51monkeys took four years for significant
59:54hair regeneration. You can't look at the
59:56data at 13 weeks for efficacy. I think
59:59that would be a huge mistake. What we
1:00:01should be looking at here is whether or
1:00:03not the prolactin receptor antibodies
1:00:06are safe. What are people reporting in
1:00:08terms of fertility markers, libido
1:00:11markers, anything else that's an adverse
1:00:14event of interest? That is what's most
1:00:16important at this read. Even if hair
1:00:19counting data looks flat or slightly
1:00:21negative, I am not discouraged by that.
1:00:23It is 13 weeks, so give it more time.
1:00:26Speaking of time, if you are fighting
1:00:28hair loss, you have to make do with the
1:00:30treatments that are available today. And
1:00:33if you're interested in pursuing
1:00:34treatments that are hyperpersonalized
1:00:36and evidence-based, I helped co-found
1:00:38the brand ULO, that's ul.co,
1:00:42to facilitate access to those
1:00:44treatments. We're a US-based teleahalth
1:00:46brand focused exclusively on hair loss.
1:00:49And we deliver what I would consider an
1:00:51unrivaled level of personalization to
1:00:53make sure you're getting the best
1:00:54possible outcomes that respect your
1:00:56needs, but also your preferences. We
1:00:58have lowd dose formulations of topical
1:01:00finasteride and topical dutastride.
1:01:02their full strength counterparts. We
1:01:04have topical minoxidils paired with
1:01:06retinoic acid or tininoan. We offer high
1:01:09strength oral dutastasteride, standard
1:01:11dose oral dutastasteride, standard dose
1:01:13finasteride, and a lot of other options
1:01:15to help facilitate your journey. I hope
1:01:18you check out the brand and in the
1:01:19meantime, we'll keep making content like
1:01:20this. I hope you enjoy it. I look
1:01:22forward to next

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