SM04554 Phase 2 results

[Chrisolution]

1~3 years

Ehhh... thanks

 

[Blackber]

I wonder why they haven't launched trials in Japan to speed up time to market, as phase ii has finished now they could have been releasing in Japan imminently

I believe those new Japanese regulations only apply to cell based therapies. It would not apply to SM.

 

[distracted]

Well the reason this drug was never made in the black market like others is that Samumed gave three different formulations. Maybe they'll release the correct one after Phase 2? That'd be great though knowing Kane it would be $100/dose

 

[nameless]

No sense in speculation now really as we'll have results soon guys..

Nonetheless a bit of hair follicle biology;

In late telogen (resting phase) before the anagen phase dermal papilla cells activate WNT signalling. There is a point of "no return" and this occurs when secondary hair germ cells turn on WNT signalling and start to proliferate. Voila, anagen initiation. Obviously there is a plethora of complex signalling occurring in between, but WNT does play a very central role in telogen to anagen transition.

Huh? So modulating WNT should be our cure right?

False, it's not that easy. The above explanation is only in a healthy hair follicle cycle.

In fact and I quote;



Yes guys, it's easy to induce anagen in healthy hair follicles which are sitting in telogen. It's easy as hell. In fact I put many treatments into that route. Indeed, even prostaglandins are known to do this since a long goddamn time. As such PGF2A for instance works good on the eyebrows for example. Why? Because it most likely modulates the hair follicle cycle. The hairs there are different from scalp hair (way shorter anagen phase and longer telogen phase and higher telogen %). Thus PGF2A most likely modulates this by extending anagen and shifting more hair follicles into the anagen phase from telogen. Resulting in more and thicker and longer hair. Simply because much resting hair follicles are prompted into anagen and subsequently the hair follicles have a longer time to grow before they fall out. Basically competent telogen hair follicles sit in a sort of equilibrium between growth arrest and proliferation.

But this is no art boys.. Bottom line is around 8-15% of hair follicles are sitting in telogen on your scalp. In Androgenetic Alopecia however telogen gets longer and also shifts to a more telogen %. But modulation of the hair follicle cycle is not what we want. We want something that saviors those miniaturized hair follicles which are in some sort of permanent arrest!

:box: Androgenetic Alopecia is dominating us all thus far guys, pray to the hair gods :notworthy. It's time for better treatments!

A couple things...

1. One of the reasons I'm high on Samumed is their report that they produced new follicles, which seems to disprove your point.

2. You say that the miniaturized follicles are "in some sort of permanent arrest" but that statement doesn't really have any scientific value or support. It isn't the kind of hard science point that you usually make. It sounds anecdotal. What does "some sort of permanent state of arrest" mean? Based on the Upjohn company's studies where they got better regrowth with minoxidil + Finasteride in Macaques than with either product alone, thereby awakening at least a few more follicles with both products than with either product alone, I think that what you're calling a "permanent state of arrest" is really just a case of some follicles being more unhealthy and needing more potent therapy in order to become healthy again.

3. My one scientific concern with SM04554 is that I don't understand how it can be expected to keep working if they cease using it after 3 months. This is really nagging at me. I read an identical-twin study a long time ago wherein one twin lost his hair but the other didn't because he had been castrated. Scientists knew that since the bald identical twin's hair had reached the point that he lost it that meant the other twin's hair had also reached that point, and the only reason he hadn't lost it is because he'd been castrated. So the scientists exposed the twin with hair to testosterone and his hair started falling out, but instead of taking years to fall out it fell out in weeks or a few months. Based on this it seems to me that even if SM04554 manages to get hair to grow you should lose that new hair in a few months unless you keep applying the SM04554. When you stop using minoxidil you lose any new hair you gained from the minoxidil, same for finasteride, dutasteride, and RU58841.

But Wilma Bergfeld is on the Samumed team and I can't imagine that she doesn't have an answer to this issue. I just can't imagine what that answer would be because when you stop using any hair loss treatment I've ever heard of then the androgens start taking your hair again.

I know I sound more optimistic everywhere else I've posted but that's just because Samumed is giving off a lot of positive signals. And even now they're giving off more positive signals. For example, we now know that they submitted their information to the AAD at least a few months ago so they've had their final phase 2A data at least a few months. It seems logical that if that data is bad they would have shut down their phase 2B, so why aren't they doing that? I interpret the fact that they're continuing their phase 2B even after they have the final results from their phase 2A to be a positive sign, but maybe they're just irresponsible with their money. I can't imagine how they would be able to keep any new hairs growing after cessation of the treatment. Even people getting success with RU58841 will lose their new hair if they stop using RU58841 because the androgens will start damaging their hair as soon as they stop using RU58841. This talk of stopping SM04554 after 3 months sounds very implausible to me. This has me very worried. I'm just hoping that there's something about the science that I don't understand and I'm basing that hope on all of the positive signs coming from Samumed. If their phase 2 results are minoxidil-like or worse why aren't they just pulling the plug on the SM04554 program?

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I'm not going to get into an argument and won't post in this thread again until the conference, but do you think the product is just going to appear on shelves if/when phase III is complete? There's more to releasing a product than just the clinical trials. Yes, Samumed has moved fast, but we don't know when the final trial might start, what goes into producing the drug, etc. I'm saying 3 years as a conservative guess if thy start phase III the 2nd half of this year - but lets wait to see what they say.

As for Replicel and Histogen - if Samumed has promising results, they're not waiting around for either of those companies when both have taken years and years to progress. Replicel has faced delay after delay, and the 2018 target is for Japan anyway (and Histogen would be released in Mexico first, ideally). I'm not holding my breath for either, at least until we see 6+ month shots from Replicel. Their initial photos were unerwhelming - I'd rather just get a hair transplant.
All I'll say is, expect to be ****ed if you're holding your breath for either of those.

Three years is not a conservative estimate for SM04554 if it's a breakthrough. If it's a breakthrough it would probably start phase 3 by September and it would take a year to go through phase 3...then about 6 - 9 months to approval (if it's approved)...then 2 - 3 months to launch. You're looking at about 2 years *if* the product works better than what's already available. If it doesn't work better than what's available then it might not even go on to phase 3, and then I'm saying goodbye to everyone here and getting a hair transplant. And if it does work better than what's available then it might be able to skip phase 3 depending on the outcome of the 21st Century Cures Act.

 

[kiwipilu]

@nameless
As far as I know current treatments awake/reactivate existing hair follicles which are sensitive to DHT.
Like you say SM04554 is supposed to produce new follicles. naivety makes me believe those new follicles are not prone to dht. Wake up call on 5th of march!?

 

[Swoop]

A couple things...

1. One of the reasons I'm high on Samumed is their report that they produced new follicles, which seems to disprove your point.

2. You say that the miniaturized follicles are "in some sort of permanent arrest" but that statement doesn't really have any scientific value or support. It isn't the kind of
hard science point that you usually make. It sounds anecdotal. "What does "some sort of permanent state of arrest" mean? Based on the Upjohn company's studies where
they got better regrowth with minoxidil + Finasteride in Macaques than with either product alone, thereby awakening at least a few more follicles with both products than
with either product alone, I think that what you're calling a "permanent state of arrest" is really just a case of some follicles being more unhealthy and needing more potent
therapy in order to become healthy again.

Nameless,

1. Are you serious here? Just because they say that they can produce new hair follicles disproves my point of actually asking for evidence for that statement? Haha, this neglects one of the most important aspects of science nameless. So I ask you where is the evidence for such a statement in actual human subjects? Can't provide it? Jup, that's what I thought. It isn't true until proven otherwise.

Oh btw may I remind you what Follica tried in their clinical trial? Dermabrasion + WNT inducing compounds + Covering the wound with hydrogel? They failed in "creating" new hair follicles.

2. I called it that way, yes. You don't understand the underlying message there. I made that post so people can understand the difference between a healthy hair follicle and a miniaturized hair follicle. And yes, one could say that a fully miniaturized hair follicle is in a permanent arrested state because it doesn't cycle anymore, while a healthy hair follicle does cycle. Subsequently it's extremely hard to reverse miniaturization while it's extremely easy to induce anagen in a healthy hair follicle when it is in telogen. As such;

Read the left. What do they say? Follicular miniaturization leads to arrest in telogen. I don't exactly like to call it arrest in "telogen", because a miniaturized hair follicle doesn't reflect how normal telogen is.

Also I don't agree with your reasoning that it's really just a case of some follicles being more unhealthy and needing more potent therapy in order to become healthy again. You make it sound so easy :roll:.

Cells for instance can irreversibly arrest themselves. Here have a read for instance; http://www.nature.com/nrm/journal/v8/n9/full/nrm2233.html.

Cells continually experience stress and damage from exogenous and endogenous sources, and their responses range from complete recovery to cell death. Proliferating cells can initiate an additional response by adopting a state of permanent cell-cycle arrest that is termed cellular senescence.

A picture that goes with this;

 

[Pavi]

Why can't this community ever wait it out and see! We don't know what's going to happen. I agree that they must have some solid results or they wouldnt be presenting their product at such a big event

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This forum is way better than bald truth except for its depressing vibe! Everyone in bald truth are way more excited. They are cautiously optimistic, like we all should be!

 

[IvanXproject]

Well the reason this drug was never made in the black market like others is that Samumed gave three different formulations. Maybe they'll release the correct one after Phase 2? That'd be great though knowing Kane it would be $100/dose

Hopefully they will release the correct one after phase 2

 

[Abu Hairy Al-Forhedi]

Why can't this community ever wait it out and see! We don't know what's going to happen. I agree that they must have some solid results or they wouldnt be presenting their product at such a big event
!

It doesnt mean anything really. They all blow these sort of events because of investors.

 

[kiwipilu]

It doesnt mean anything really. They all blow these sort of events because of investors.

SAMUMED don't only attend here, they are supposed to release the phase II trial results(Safety, Tolerability and Efficacy). for investors to be interested in SM, the results have to be significant. If they attend this meeting, results should be significant,and significantly good.

 

[Agustin Araujo]

I am hoping SM04554 is many times better than Minoxidil at regrowing and maintaining hair. :listen:

 

[Pavi]

It doesnt mean anything really. They all blow these sort of events because of investors.

Makes no sense..... So you think they're just gonna present average date in order to get investors?

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I am hoping SM04554 is many times better than Minoxidil at regrowing and maintaining hair. :listen:

How well do u think min maintains hair now

 

[Swoop]

I want to add to this by the way nameless that I don't know how well this compound performs obviously. I would be pretty surprised if it outperforms minoxidil though. We'll know very soon anyway, that's the great thing. One can only hope for the best.

If it does work significantly better than minoxidil then it will create massive attention. Less than 2 weeks and we'll know!

 

[I.D WALKER]

Eleven days 14 minutes 17 seconds to be precise, but who's counting? LOL

I want to add to this by the way nameless that I don't know how well this compound performs obviously. I would be pretty surprised if it outperforms minoxidil though. We'll know very soon anyway, that's the great thing. One can only hope for the best.

If it does work significantly better than minoxidil then it will create massive attention. Less than 2 weeks and we'll know!

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Sorry to throw you guys another wet blanket., I seem to recall it was thought to be more effective for older persons who are balding later in life.

If someone could confirm/contest this I would appreciate it.

 

[Breyfogle]

Swoop you're great but it's hard to take you seriously with that avatar.
Is that you? What's wrong with your nipples?

 

[nameless]

Just curious, since I value your opinion - why would they say it's poised to move into Phase III if it wasn't at least on par with minoxidil? I guess it could work on a more consistent % of trial patients and in turn be worth bringing to market, but I don't get why they'd spend the money to bring out a prescription drug that is no more effective than something that can be bought over the counter, and likely cheaper.

Very very good point. If it's not more effective than minoxidil then they're crazy if they waste anymore money on it. What with doctor visits and all, getting a prescription drug is more costly and burdensome than getting an OT treatment so if SM04554 is no better than minoxidil then Samumed should just pull the plug on it. But it's still active in Phase 2B. So isn't this a positive sign?

 

[AbuAktar]

Swoop you're great but it's hard to take you seriously with that avatar.
Is that you? What's wrong with your nipples?

looks like gyno to me

 

[Blackber]

Eleven days 14 minutes 17 seconds to be precise, but who's counting? LOL

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Sorry to throw you guys another wet blanket., I seem to recall it was thought to be more effective for older persons who are balding later in life.

If someone could confirm/contest this I would appreciate it.

Histogen is the company that said they had even better results with older patients, not SM.

 

[nameless]

I want to add to this by the way nameless that I don't know how well this compound performs obviously. I would be pretty surprised if it outperforms minoxidil though. We'll know very soon anyway, that's the great thing. One can only hope for the best.

If it does work significantly better than minoxidil then it will create massive attention. Less than 2 weeks and we'll know!

I know you want it to perform well Swoop. And you're right that we should wait for evidence of new follicles because that's too big of a claim to accept at face value. We need proof. I'm just getting excited is all. I'm very concerned about the issues you've raised and also how they could possibly keep the follicles growing hair after cessation of treatment (after 3 months) unless (drum roll please) what if SM04554 causes some kind of permanent or long term activation of Wnt that stays activated even after cessation of treatment?? Does this seem plausible?

I'm also concerned about their use of the word "significant" to describe the improvement in their preliminary phase 2A results.

 

[Swoop]

Just curious, since I value your opinion - why would they say it's poised to move into Phase III if it wasn't at least on par with minoxidil? I guess it could work on a more consistent % of trial patients and in turn be worth bringing to market, but I don't get why they'd spend the money to bring out a prescription drug that is no more effective than something that can be bought over the counter, and likely cheaper.

Hemo, very good point. If it indeed does proceed to phase 3 then it has potential and that is definitely a good reason to get at least somewhat excited imo. BUT, is this 100% confirmed? Cause the latest paper mentions that they "plan" to move to phase 3. Doesn't sound like a confirmation to me? Would be great obviously as it has been a very long time since any hair loss treatment has hit phase 3 trials.

Swoop you're great but it's hard to take you seriously with that avatar.
Is that you? What's wrong with your nipples?

What is wrong with them? I like them man! This is from a while ago; http://s28.postimg.org/qouwktjcd/older15.jpg. Weak brittle hibernation state there while being at higher bf%.

If you really want I can send you that picture from my avatar later in a way higher resolution so you can have a actual proper look at my nipples and have a quick wank :jackit:? Just PM me if you want to have it. I'll provide it anytime man if that makes you happy. Let's stay on topic here though.