Sm04554

[Swooping]

I really feel that samumed has got a product that at the very least will be an additional to add to our arsenal. I was looking at their additional round of phase 2 study with the punch biopsy. I was curious to see what exactly they were looking to evaluate from the tissue biopsy in terms of biomarkers. straight from the clinical trials page they are aiming to evaluate the following:

Change in nuclear expression of beta-catenin
Change in nuclear expression of Ki-67 in epidermis and hair follicles.
Change in Ki-67 index in epidermis and hair follicles

First off beta catenin, I believe we all understand at this point if we follow the thread that it has direct affect on wnt pathway and therefore blah blah blah. Basically it can be very important in reactivating our dead beat hair follicle cells that don't want to do their job anymore.
However, I was curious to look into the Ki-67 biomarker they were interested in. I looked at what exactly Ki-67 protein is for and straight from wikipedia:

"The Ki-67 protein (also known as MKI67) is a cellular marker for proliferation.[5] It is strictly associated with cell proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. Ki-67 protein is present during all active phases of the cell cycle (G1, S, G2, and mitosis), but is absent from resting cells (G0)"

(G0) is = senescent phase where nothing is happening. Whereas previous studies have shown that our hair follicle cells experience longer and longer phases of G0 and shorter phases of interphase and mitosis, until ultimately permanently senescent and unfortunately slick bald.

All this coupled with the fact they recruited high norwoods, had a huge first phase 2 study, decided to run another smaller phase 2 study with biomarker biospy evaluation simultaneously with their first phase 2 study, and are evaluating these biomarkers which are directly linked to cell proliferation seem to all point to a positive opposed to a negative. Of course this is all speculative and we will have to wait a few more months to see just exactly the results are.

Thanks, valuable and interesting information. The consensus between many researchers is basically that senescence/cell cycle arrest and apoptosis (or combination of both) finds place in DPC. DPC size and amount modulates hair follicle size. A decline of DPC leads to a smaller hair follicle. In fact the DPC act as a master instructive niche for the whole hair follicle.

I have once illustrated this in a picture so it gets more clear. (Please do note that this isn't the exact pathway chain but just a overall general view)



Factually this explains why AGA is so extremely heard to reverse. A major pathway like P53 possibly sets in who is a master of diverse cellular processes and is a evolutionary ancient coordinator of stress responses. When damage is done it can literally lock down a cell for instance and keep it that way. These pathways are very complex and versatile though. P53 and P21 for instance can activate hundreds of downstream genes and have many functions.

However the beauty of a chemical like SM04554 is that while it acts directly on b-catenin (wnt pathway) it might actually crosstalk with major regulatory pathways like P53 and other major regulatory pathways.

Purely looking at it from a theoretical perspective is that it could work really good in my opinion. Furthermore we have no observational evidence of any direct b-catenin agonist simply because there has never been used one on humans ever. At least AFAIK.

Let's hope we will get positively surprised. Hopefully they will release their results asap.

[nameless]

I just tried to talk with Samumed. They're very paranoid and secretive. They won't even discuss the phase 2 that has almost completed. They did say that they do not know yet if SM04554 works or not.

[nameless]

Hello all, new to the board here.

Start this trial today (USA). The doctor is extremely encouraged by the potential of this treatment, although the clinical research nurse with whom I spoke said she hasn't witnessed much growth in the patients she has seen thus far.

We shall see.

The study didn't even start until November 2014. Your first post is late January 2015. That means that your first post is 2 - 3 months after the study first started. I would not expect that a lot of patients would be seeing regrowth by the time you started.

[nameless]

This is getting close to completion isn't it? I thought it was done by around November?

will be very interesting to see the results.

The study purportedly ends in October 2015.

What are the dates for the 2015 hair loss congress in Miami?

[Arieux]

@ nameless: Congress will be in November 18-21. (http://www.hair2015.org/)
Samumed is one of the most important sponsors (silver).
All of that can't be only pure coincidence in my opinion.

[nameless]

@ nameless: Congress will be in November 18-21. (http://www.hair2015.org/)
Samumed is one of the most important sponsors (silver).
All of that can't be only pure coincidence in my opinion.

so the first phase 2 ends about 1 month before the 2015 congress. Interesting. They could have the phase 2 results by the time the 2015 congress begins. They will at least have some preliminary data. It seems to me that they should know if the drug works by then or not.

[JayM]

I just tried to talk with Samumed. They're very paranoid and secretive. They won't even discuss the phase 2 that has almost completed. They did say that they do not know yet if SM04554 works or not.

Tbf if they aren't going to say anything then they are probably going to say that aha.

[lacazette]

I really believe in samumed, if it really works (like in studies with new HF formation from existing ones) even a high Norwoods will be able to undergo a big hairtransplant with a decent result
If Samumed give me my hair life back , I will tatoo them upon my heart hehe

I really hope they are planning the asian market already, and that this seconde phase 2 with biomarkers could be sufficient for a future release there (cause 'im afraid it can't be the case in US as the 21st cure bill will take months to become reality). i can't wait too long before testing this Wnt activation!

[macbeth81]

I just tried to talk with Samumed. They're very paranoid and secretive. They won't even discuss the phase 2 that has almost completed. They did say that they do not know yet if SM04554 works or not.

Shouldn't they technically not know if it works or not if this is a double blind study? Neither the subject or investigator should know if they received SM04554 or placebo until conclusion.

Of course practically speaking it should be obvious if patients are returning with cosmetically visible, to the plain eye changes in hair density.

I find it surprising that they would initiate a second Phase 2 without knowing even the possibility of success. However, they do seem to be money rich. They even have their own D.C. lobbyist. I am not sure if this is common for small biotechs or not.

Lobbyist Registration

[nameless]

Shouldn't they technically not know if it works or not if this is a double blind study? Neither the subject or investigator should know if they received SM04554 or placebo until conclusion.

Of course practically speaking it should be obvious if patients are returning with cosmetically visible, to the plain eye changes in hair density.

I find it surprising that they would initiate a second Phase 2 without knowing even the possibility of success. However, they do seem to be money rich. They even have their own D.C. lobbyist. I am not sure if this is common for small biotechs or not.

Lobbyist Registration

I agree with you that technically they should not know for sure if the treatment works or not, but like you said it seems like they would be able to perceive if some patients are obviously growing hair. So yes, I do think that they probably know if their drug works or not. And *if* they do know that their drug does not work then it makes no sense at all that they would waste more money on the supplemental study that they just initiated.

[JayM]

American guys - has there been any news on 21st century cures act?

[It's2014ComeOnAlready]

American guys - has there been any news on 21st century cures act?

Will be voted on early next year. I read an article posted yesterday, where a group of senators and congressman tied closely to the bill, speaking to a group of people, saying that they "guarantee it will become law."

[JayM]

Thanks 2014. Could you post the article?

[hellouser]

Will be voted on early next year. I read an article posted yesterday, where a group of senators and congressman tied closely to the bill, speaking to a group of people, saying that they "guarantee it will become law."

Why not just implement it now and stop wasting time?

[It's2014ComeOnAlready]

Thanks 2014. Could you post the article?

http://energycommerce.house.gov/icymi/%E2%80%9Cgroundbreaking-research-offers-best-hope%E2%80%9D