Samumed sm04554. Only drug on phase 3

[Gegen]

That's what GSK3b is

Not really, GSK3b is downstream of the bind between Wnt and Frizzled. Not upstream as I said.

In conversation with Samumed CEO Osman Kibar: Drugging Wnt, restoring youth and unconventional capital

Founded in 2008, Samumed has spent most of its lifetime working under the radar. | Samumed CEO Osman Kibar discusses regenerative medicine, drugging the Wnt pathway and his company's unorthodox journey.

www.fiercebiotech.com

"What’s more, hitting Wnt receptors hard can backfire. A drug may have its intended effect, but it may disrupt other processes, leading to side effects and safety concerns. So, instead of aiming at Wnt receptors on the cell membrane, Samumed’s drugs target CLK and DYRK, kinase enzymes that are upstream of the Wnt pathway. "

I was talking about the modulation of CLK and DYRK.

 

[pegasus2]

Not really, GSK3b is downstream of the bind between Wnt and Frizzled. Not upstream as I said.

In conversation with Samumed CEO Osman Kibar: Drugging Wnt, restoring youth and unconventional capital

Founded in 2008, Samumed has spent most of its lifetime working under the radar. | Samumed CEO Osman Kibar discusses regenerative medicine, drugging the Wnt pathway and his company's unorthodox journey.

www.fiercebiotech.com

"What’s more, hitting Wnt receptors hard can backfire. A drug may have its intended effect, but it may disrupt other processes, leading to side effects and safety concerns. So, instead of aiming at Wnt receptors on the cell membrane, Samumed’s drugs target CLK and DYRK, kinase enzymes that are upstream of the Wnt pathway. "

I was talking about the modulation of CLK and DYRK.

They had a slide that specifically said it inhibits gsk3b.

 

[Gegen]

They had a slide that specifically said it inhibits gsk3b.

Where ? Sorry to look like an interrogator lol. But I searched many times this slide you talked about and never found it.

Only thing I found is that thread on baldtruthtaIk : https://www.baldtruthtaIk.com/threads/15455-Sm04554 Where some people say that it might be a GSK3 inhibitor.

 

[pegasus2]

Where ? Sorry to look like an interrogator lol. But I searched many times this slide you talked about and never found it.

Only thing I found is that thread on baldtruthtaIk : https://www.baldtruthtaIk.com/threads/15455-Sm04554 Where some people say that it might be a GSK3 inhibitor.

It's not on their site anymore.

 

[Gegen]

@Gegen how much hair growth do you expect in the phase 3 study? Do you think the effect will continue to have an effect beyond a year (e.g. growth over two years if you continue to take it daily)

I don't really know. I'd say that as long as you use it, hairs will grow, if we keep in mind that Samumed wants to create de-aging effects. So their drugs have to get a long term effect. Or maybe SM04554 will have a threshold of efficiency, and then I'll sound like a delusional idiot. We have no assurance on this question.

Also, I think that like in the second test phase, "young" people with relatively "low" Norwood will have much greater hargrowth than older people. And this is the main reason I wait for this stuff, as I'm 19 and NW2/2,5. The optimal population wich had OK-tier results (between 20 and 30 new hairs per square centimeter after 135 days, wich is the range of good minoxidil responders) were under 45 and NW4, so I do not hope it will cure me but at least help me a lot.

So, we don't really know how it works, as the slide that evoked GSK3b inhibition has been deleted for a reason ( maybe it was deleted because the mechanism is more complex ). And as long as we don't know how it works/we don't have a longer study than only 3 months, we can only speculate and imagine the sm04554's effects over 1 year and more.

Let's be a little more patient, phase 3 results are coming soon, it's a matter of months now !

 

[NorwoodGuardian]

I don't really know. I'd say that as long as you use it, hairs will grow, if we keep in mind that Samumed wants to create de-aging effects. So their drugs have to get a long term effect. Or maybe SM04554 will have a threshold of efficiency, and then I'll sound like a delusional idiot. We have no assurance on this question.

Also, I think that like in the second test phase, "young" people with relatively "low" Norwood will have much greater hargrowth than older people. And this is the main reason I wait for this stuff, as I'm 19 and NW2/2,5. The optimal population wich had OK-tier results (between 20 and 30 new hairs per square centimeter after 135 days, wich is the range of good minoxidil responders) were under 45 and NW4, so I do not hope it will cure me but at least help me a lot.

So, we don't really know how it works, as the slide that evoked GSK3b inhibition has been deleted for a reason ( maybe it was deleted because the mechanism is more complex ). And as long as we don't know how it works/we don't have a longer study than only 3 months, we can only speculate and imagine the sm04554's effects over 1 year and more.

Let's be a little more patient, phase 3 results are coming soon, it's a matter of months now !

Prepare for a delay in hairloss field.

 

[pegasus2]

People don't realize this, but minoxidil upregulates the canonical Wnt pathway too. I would expect the same sort of curve from SM that we see from minoxidil. There will probably be a greater response rate, but I don't think the effect will last any longer than minoxidil, which peaks around one year.

 

[Gegen]

People don't realize this, but minoxidil upregulates the canonical Wnt pathway too. I would expect the same sort of curve from SM that we see from minoxidil. There will probably be a greater response rate, but I don't think the effect will last any longer than minoxidil, which peaks around one year.

Yes, I knew that minoxidil upregulated Wnt by phosporylating GSK3b (maybe the cause of collagen loss when using Minoxidil ?) and two other enzymes involved in Wnt pathway wich I don't remembers the names.
But at what intensity compared to SM ? Also, if SM was so similar to minoxidil, regrowth would not have continued after stopping treatment in the phase 2 study, at least from my knowledge in matter of hairloss.
I think Samumed's scientists know something we don't, and it is for that reason they bet so much on WNT pathway regulation. But it is only speculation.

Edit: https://pubmed.ncbi.nlm.nih.gov/21524889/
the two other enzymes are PKa and PKb.

 

[Gegen]

Prepare for a delay in hairloss field.

For the commercialization, yes probably, but for study results we know that it is for soon.

 

[pegasus2]

Yes, I knew that minoxidil upregulated Wnt by phosporylating GSK3b (maybe the cause of collagen loss when using Minoxidil ?) and two other enzymes involved in Wnt pathway wich I don't remembers the names.
But at what intensity compared to SM ? Also, if SM was so similar to minoxidil, regrowth would not have continued after stopping treatment in the phase 2 study, at least from my knowledge in matter of hairloss.
I think Samumed's scientists know something we don't, and it is for that reason they bet so much on WNT pathway regulation. But it is only speculation.

Edit: https://pubmed.ncbi.nlm.nih.gov/21524889/
the two other enzymes are PKa and PKb.

I wasn't speaking to you specifically, but to the people who don't know that. There are dozens of mechanisms by which minoxidil works, it pretty much hits on everything in the Wnt pathway. That's why nothing has beaten it yet. We only have one short study for SM, and it showed somewhat less regrowth than minoxidil. Time will tell if that finding that regrowth continued for 3 months after discontinuation can be replicated. I find it wishful thinking to believe it would continue much beyond that when the AR is continually being activated. A lot of scientists bet on things that don't work out. Ask Allergan how their bet on setipiprant worked out, or ask Aclaris how JAK inhibitors worked out for Androgenetic Alopecia. The Wnt pathway is the key to hair loss, but what reason do we have to believe that their method of activating it is any more potent than other Wnt activators? Unless their drug works downstream of Wnts to induce beta-catenin then there are a lot of dysregulated genes that it has to fix. It's not going to be a miracle treatment. I'll bet anyone that it will not outperform minoxidil in the phase 3 trial.

 

[pegasus2]

Also imagine what this molecule could do in conjunction with needling.

Buy it and find out, or buy CHIR99021 which is probably a more potent Wnt agonist.

 

[Tom4362]

I'll bet anyone that it will not outperform minoxidil in the phase 3 trial.

I would be ecstatic if it grows as much hair as minoxidil and will then maintain what you have without the sides

 

[pegasus2]

I would be ecstatic if it grows as much hair as minoxidil and will then maintain what you have without the sides

I would be happy with that too, but it's not going to happen.

 

[nick123]

I'll bet anyone that it will not outperform minoxidil in the phase 3 trial.

Interesting you say this because surely minoxidils efficacy is directly dependant on the level of sulfotransferase enzymes, so surely there would be some people with low sulfotransferase enzymes where for them SM04554 outperforms minoxidil?

Just to add I'm not deluded in thinking that SM04554 is going to be some amazing regrowth treatment but there's just such a limited amount of FDA/EMA approved treatments I'd be happy with something that helps long term (fingers crossed). Not everyone is comfortable enough to throw the research chemical kitchen sink at their scalp.

 

[pegasus2]

Interesting you say this because surely minoxidils efficacy is directly dependant on the level of sulfotransferase enzymes, so surely there would be some people with low sulfotransferase enzymes where for them SM04554 outperforms minoxidil?

Just to add I'm not deluded in thinking that SM04554 is going to be some amazing regrowth treatment but there's just such a limited amount of FDA/EMA approved treatments I'd be happy with something that helps long term (fingers crossed). Not everyone is comfortable enough to throw the research chemical kitchen sink at their scalp.

That's the thing that really shows how potent minoxidil is. Half the people don't respond to it, yet it still outperforms everything else in clinical trials. The hair growth numbers would be twice as high for minoxidil if they used minoxidil sulfate. Unfortunately that's not practical for distribution. If you are a responder to minoxidil then it's far more effective than anything else out there. If you aren't a responder, get minoxidil sulfate powder and mix it yourself, or use oral minoxidil. You'll do better than with SM, I guarantee it.

 

[Tom4362]

I would be happy with that too, but it's not going to happen.

Can you elaborate on why you think that?

 

[Gegen]

@Gegen
Do you think they will publish before/after Pictures?

That is a question I can't answer.

 

[theotherusero]

Since SM04554 is available on kane, why no one is using it? There are no info on dosage and vehicle or there are other problems?

 

[Gegen]

Since SM04554 is available on kane, why no one is using it? There are no info on dosage and vehicle or there are other problems?

If my memory is good, vehicle is a problem. Ask JohnDifool, he tried it and said it's not very effective on this thread : https://www.hairlosstalk.com/intera...-results-normalized-to-baseline.125705/page-9

 

[pegasus2]

Since SM04554 is available on kane, why no one is using it? There are no info on dosage and vehicle or there are other problems?

People have used it, and nobody noticed a great improvement on it so they gave up. It takes 3-6 months to notice any change, and most people don't wait that long. Everyone is looking to go back to a NW1 in two months, and when they don't they give up and say it doesn't work. It's a matter of expectations. It's probably working for them, but a 10% difference in hair growth on the vertex is not that easy to see. Anyways, there are more potent Wnt agonists out there. SM is probably safer, but less effective than others.