Breezula update 2022 June apparently they are doing trials very soon

[lukedorian]

upon a quick google search I found a surprising amount of people on reddit that have experienced systemic side effects from winlevi. many women having absent periods, weight gain etc.

thats crazy and sad. I was looking forward to CB and it has been praised since 2014, a crazy long 9 years now that its been studied. it stands for this industry like nothing else. 10 years of research for an extremely expensive product that works worse than finasteride, needs to be topically applied twice a day and still has systemic side effects in quite a few people. no long term data.

i realize they updated their website for phase 3 trials in 2023 H1 but I dont think they even need to do them anymore. this is a failed product. and I also dont believe Kintor anymore either, they have developed their drug with zero intelligence, its not targeted for skin at all, its just a f*****g RU analogue 20 years later. they have not even put a thought into the vehicle which is kind of insane if they use ethanol pg then they are officially a clown company. also zero confidence in their degrader.

what Kintor WILL achieve though is to make is even LESS attractive for other companies to develop truly innovative and solid products even for maintenance(not even that is possible in 2023). I really hope Kintor and sun pharma will go financially bankrupt before any of the drugs come out. because if they do, the game is over for new drugs within the next 10-15 years.

its actually crazy how little progress there has been made. every hype has been totally destroyed, its almost iconic at this point. not almost, it IS iconic.

I think its very rare to find a field where as a patient you are basically stuck with drugs from another century. I think there is none actually, sure other diseases are much worse and also underfunded and studied but there have been new drugs still. for this there has not been anything. its a meme at this point

I haven’t found anything to be honest but listen i was replying as i was reading thru the thread, the vehicle thing might be an issue, when i read it , it makes a lot of sense, when ever i search for experiences with CB i don’t find much tbh, just wanted to share mine since i used it non stop for a whole year, today 8 days off it i notice how my muscles get harder, i sleep way better, also have a boost in libido (i know i said my libido was not affected) and my waist line and chest are getting tighter, i was like holding fat/water around those areas, legs are getting fuller, i’m kinda ectomorph type and my legs have always been my weak point but i have some growth over the years of intense training.
also you are right when stating that there is no such a thing as pharmaceutical cb since it is not out yet, i get it from a compounding pharmacy in my country and they say they perform thorough 3rd party testing which i believe but we’ll have to wait on Breezula to judge, that is what i’ll do.
i never used any of these things by them selves i always mix it with minoxidil.
Regarding the trials/studies and such read you get sides from 5AR inhibitors as most of us and according to Merck only 2% of men experienced sides, it seems like biased data, seeing all the reports of men getting them.
i am feeling better and better as the days pass almost to the point to of not doing any labs, i know i have 0 LH and FSH since i’m on trt already dialed in so…
i won’t use CB nor Pyrilutamide again until they are available to the public and not from grey market.
Saw great things from topical finasteride specially getting rid of my oily forehead with a very small amount, P-3074 study, this is the one we have in our country, but then again i felt i got sides because it was mixxed with cb and minoxidil
i’ll wait 2 weeks off CB to give it another try and that is pretty much it
For now RIP CB and Pyri for me, a dermatologist i follow on youtube that takes part on updates on these drugs (like a close door updates not available to the public) said recently that there was at least 1 case of “central suppression” with pyrilutamide i don’t really know what he meant by that but he also said he could not disclose anything else.
after all these years trying sh*t (on finasteride since 2014) i know that if there is a very small percentage of people getting sides with these type of drugs i for sure am in there lol.

 

[Min0]

You need your cortisol also tested, your Estradiol is low, Estradiol is a big player in maintaining libido, you also need sexual hormone binding globuline levels tested, judging by LH, FSH you are not suppressed but they are still on the lower end
You 2 might be right after all and come from a state of Suppression, you only need time

like i said, the doctor seemed dismissive, he was like : "just stop taking these drugs and you'll get better bruh"
but i do feel better each day now indeed.
and my hair has started falling again ;_;
what do you think about fluridil ? i just bought a two month supply of it, not sure if i should try it or not

 

[mooreu]

@lukedorian

The vehicle is probably the key to eliminating or lessening the side effects of clascoterone. In 2018 I added the powder directly to a solution (Kerastase) and I had sides. In 2021 I purchased a pre-mixed solution with Trichosol as the vehicle and again I had sides. If someone is going to trial it I suggest mimicking the vehicle that was used in the clinical trials. I may try it again but only once it's commercially available. In the meantime I'm back to using spironolactone cream (can't tolerate topical finasteride or dutasteride).

 

[badnewsbearer]

well i was thinking of something a little more advanced like nanoparticles not trichosol or whatever. i think chitosan coating can help snd there is good studies on that.

androgenic alopecia is a localized skin disorder, it is not a sysmetic disease and we want local effect of drugs. it only makes sense to have a delivery mechanism that keeps it as much local as possible.

and yes cassiopea did penetration studies and all that however since people still get sixes on winlevi which is their formulation its not the be all either. there is a lot of unused reseaech out there but i seem to be the only person who digged into it and sees the promising nature of it.

also some do get it wrong, you donf want soemthing that doesnt penetrate well od that inhibits finasterides or CBs penetration. you want something that is maximally tsrgeted to the follicle so that you can use a much lower dose. imagine this:

0.2mg finasteride is enouvh to reduce dht in EVERY tissue by 60-70% even in fhe prpstate where there is so much dht, 10 times more per volume than in serum. the dermal papilla is just a small amount of cells and the dht pdoduced there is probably like 1/100th if the total dht in the body

so if 0.2mg can reduce everything by 60% and you can still find lots of unbound finasteride in the blood, how much sould be needed in theory in total isolation to inhibit 5AR in the follicle? like many many fold less. given a perfect delivery system that only nukes dht in the dermal papilla it would be possible to have full finasteride effect with zero systemic serum inhibition. and the dose could be like 0.001% IF all of it gets delivered where it should be. snd thats the problem with current vehicle. too much goes systemic and too little to the DP. the idea of nanoparticles is that they travel down the follicular shaft, lock in there and form a reservoir with slow constant release. the same idea works for pyrilutamide. if its strong enough to stop hair loss AND cause systemic sides, then Imagine how potent it would be if all the drug was kept local. i think this is extremely crucial. we are abandoning the cave man mentality of treating a local disorder with oral pills which was long overdue. however for local application we need highly targeted carriers. now we dont snd cant have the perfect vehicle but we can get a lot closer than just mixing CB and pyrilutamide into ethanol likd cave men because ethanol penetrates well. yes if does penetrate well but also it does penetrate well into the circulation. animal and human excised skin studies have shown 3-4 times less drug in the serum snd 2 times more drug on the follicular duct than with conventional carriers.

i ppsted a lot of research but it is evident to me that nobody is interested in this type of thing. i just dont get why. clearly you all care very much about this to the extent you buy reseaech chemicals and havs had terrible experiences. however it never occured to anybody that if the problem is leakage into circulation, that thaz is something that must be worked on. i think it will be necessary or we will all miss out on new drugs like pyrilutamide or GT-whatever, CB and whatever comes, siRNAs etc.

the drugs arent designed as wd thought to stay local. the vehicle has to accomplish that


the mouse study posted in the reseaech paper secrion here showed it is POSSIBLE to degrade the androgen receptor significantly in the scalp without having ANY of thr drug leak into serum. mice skin is thinner than human skin so there is a chance this applies as well.

idk how we can do it, my idea was to set something up where we go throgu studies which i have done already, approach leading experts in the field for nanoparticles and drug delivery and then find a compounding pharmacy to compound these based on the paper(bc many variables likd particle size, charge, other excipients are important)


ive seen studies with 2-3 times more drug in the follicle and 2-3 times less in circulation compared with ethanol for various drugs. ot works particularily well for dutasteride becsuse of its molecular weight and it cooperates well with the Nature of nanoparticles. they showed 5times more dutasteride with the particle, 50% of the dutasteride apploed topically landed in the follicle. imagine how small of a dose you could use if 50% of it gets directly to the follicle.

oral dutasteride is 0.5mg and enough to nuke serum dht by 90% we only want follicular dht by 50%

but i understand itll be very hard bc ex vivo studies often dont translate well to real human beings. however i think it is ppssible to delivery these drugs in theory very targeted and have hogh efficacy with basically zero systemic impact

 

[Ralph Wiggum]

Cosmo Pharmaceuticals reports record results for 2022, preliminary results exceeding guidance, increased dividend distribution and 2023 guidance

Ad hoc announcement pursuant to Art. 53 LR Dublin, Ireland – 16 February 2023: Cosmo Pharmaceuticals N.V. (SIX: COPN, XETRA: C43) (“Cosmo”) today announced its preliminary unaudited results for the financial year 2022. Total revenues of €102.1m vs. guidance of €90m - €100m, representing

www.cosmopharma.com

These record 2022 results reflect both the performance of Cosmo’s new products, Winlevi® and GI Genius™, and the performance of the company’s legacy business which has continued to grow. The clinical development pipeline has also progressed significantly, and Cosmo expects to have the first patient enrolled in the Breezula® (Clascoterone solution for androgenetic alopecia) phase III trial in males in Q1 2023.

 

[Baldingtooyoung]

for real though, is really nobody interested in vehicle research? imagine being able to use all those bullshit drugs that go systemic. making the research section actually the research section? I have provided so many papers and research, there is a massive amount of new research from 2018 to 2022 and nobody gives a rats *** about it. I dont understand it. sure its an effort to identity it, one must talk to people doing the research, find a compounding pharmacy to make it, test it, reformulate etc. but a proper delivery mechanism is very important I think.

I don't give a sh*t about the vehicle tbh. I just need to find something that works.

 

[badnewsbearer]

I don't give a sh*t about the vehicle tbh. I just need to find something that works.

a better vehicle can massively impact efficacy and side effects.

 

[Modill]

Hi @Min0, any luck with Fluridil?

By other hand, did you see that the super electric cap from Mane Biotech is already available? Anyone is going to try that?

 

[Min0]

Hi @Min0, any luck with Fluridil?

By other hand, did you see that the super electric cap from Mane Biotech is already available? Anyone is going to try that?

i have good news, i got back my full libido. and i'm already +8 days on fluridil with zero side effects. i even think that fluridil has a positive impact on my libido (less testosterone binding to follicle AR and going elsewhere perhaps ?)

now i just hope it will actually stop my hairloss at least.

i'm optimistic because i definitely respond to AR antagonists, my problem were the side effects.
fluridil seems very different from pyri and CB. my libido seems even higher while on it.

pyri and cb used to shut down my libido completely even at low doses.

 

[Modill]

i have good news, i got back my full libido. and i'm already +8 days on fluridil with zero side effects. i even think that fluridil has a positive impact on my libido (less testosterone binding to follicle AR and going elsewhere perhaps ?)

now i just hope it will actually stop my hairloss at least.

i'm optimistic because i definitely respond to AR antagonists, my problem were the side effects.
fluridil seems very different from pyri and CB. my libido seems even higher while on it.

pyri and cb used to shut down my libido completely even at low doses.

I don’t think if the state “less testosterone binding to follicle AR and going elsewhere perhaps” has any sense.

Maybe Fluridil has no effect on you, and your hairloss will continue?

 

[Min0]

I don’t think if the state “less testosterone binding to follicle AR and going elsewhere perhaps” has any sense.

Maybe Fluridil has no effect on you, and your hairloss will continue?

well let’s just wait and see then .

 

[badnewsbearer]

I don’t think if the state “less testosterone binding to follicle AR and going elsewhere perhaps” has any sense.

Maybe Fluridil has no effect on you, and your hairloss will continue?

why does it not make any sense? some people have reported increased acne in the face with stuff like pyrilutamide which indicates increased action of androgens there.

it also depends how the anti androgenic effect takes place. as I have said before, there are actually different targets of androgens and also many different androgen receptors. what pyrilutamide and RU are are nuclear receptor antagonists they bind the nuclear receptor in the cytoplasm. however there are other androgen receptors for example membrane receptors (mAR) that are also a target of DHT but they dont go into the nucleus but do other things like signal transduction or for example membrane channel openers. the reason an anti androgen might be better for libido and erections than 5AR inhibitors for example is that e.g in the case of erections a lot of the effects of the androgen are actually mediated through the membrane receptors via non nuclear effects so something like fluridil would have no effect at all on this process and since more testosterone is now unbound(the AR is occupied) to the receptor this pathway might actually be activated even more.

I dont know how it works for libido because the exact interaction between androgens and libido is poorly understood and is not as simple as in the case of erectile function(they promote relaxation of the smooth muscle by opining Ca+ channels or increase expression of eNOS and nNOS, pde5 expression etc.). so it might very well be that some anti androgens might be better tolerated than others.

however obviously hair loss is also affected by these transmembrane androgen receptors also which is why combinational therapy of a 5AR inhibitor and an androgen receptor antagonist makes so much sense. what could also work is AR degraders as these mAR splice variants often have similar coding and thus some degraders can actually degrade all kinds of androgen receptors not just the nuclear one. so this means Kintors degrader product could not just be better due to more potency but also bc pyrilutamide does not actually address the non nuclear mediated effects of DHT and other androgens.

again, the targeting is key, if you get the degrader into the circulation its sh*t so the vehicle must be very good

 

[Modill]

well let’s just wait and see then .

But hairloss feelings? Do you notice anything?

 

[badnewsbearer]

i have never read a positive report about fluridil. once again as someone who is basically the same as Min0 and Modill, I know I respond extremely well to even tiny amount of finasteride. I have managed to stop shedding completely, remove all itch and see thickening and darkening of hair after 7 weeks of topical finasteride and I managed that with only 17% reduction in serum DHT.

for me, that was not enough because I still have severe sexual sides. but I see the potential in having a targeted localized treatment when the proper vehicle and dosing regiment is used. with a better vehicle these 17% might be brought down to 5% and at that point I cant believe its physiologically possible to have side effects as it fluctuates even more heavily on a daily basis than those 5%.


i dont understand @Min0 why you would rather spend a large amount of money of fluridil which is very costly and no study supports its effectiveness than investigate how to target the drugs that DO work much more effectively to the skin so a much lower dose can be used an less goes into the circulation.

we must approach this in a more scientific manner. basically I think for everyone there is a certain dosage of anti androgens that the body can tolerate. androgens fluctate so much on a daily basis it'd be ridiculous if an infinitely small amount of drug could do that. second, these drugs have all short half lives and barely accumulate. I have used topical finasteride for 5 weeks and my DHT was changed by 16-17%. again, still too much for me sides wise but it shows that there is no accumulation. so it makes sense to maximize the ratio of the finasteride that goes to the follicle and that that goes into the circulation. im using liposomal vehicle now which is still not that great because it has high transdermal flux across the entire skin not just the follicular shunts. so if targeting was increased then the dose could be lower 2-3 fold again with same efficiency.

other than that im not very hopeful. GT will be super effective most likely but we will also get sides. all the new drugs will be targeting the androgen pathway, hutera, Olix, pyrilutamide, GT, breezula, all the most exciting new products that will make any man basically immune to hair loss won't work for people like us. we either find a way to use them or the head must be shaved. fluridil I think is not the way, it makes sense on paper and I totally get why you try it, hell I might try it as well out of desperation.

but I know super low doses of anti androgens can be effective if they are delivered right and there is promise in that dont you think

 

[Modill]

@badnewsbearer we don’t investigate vehicles because we don’t know. What you recommend for us to try?

 

[badnewsbearer]

@badnewsbearer we don’t investigate vehicles because we don’t know. What you recommend for us to try?

after my attempt with topical finasteride 0.01% liposomal and still having the same very severe sexual sides ive kind of resigned tbh. I cant say I haven't exhausted everything and tried everything and it still makes no sense for me and what I tried worked well for other people however my body just seems so strangely intolerant to it. honestly @Modill I dont know. however I know believe what you are all saying about pyrilutamide and CB and other anti androgens. the thing is, we have something that works and is very effective and in theory only needs to act locally. the real accomplishment would be to prevent it from going systemic.

there are research vehicles like nano structured particles that could on paper help but its quite hard to obtain and after seeing how I didn't even see a mild improvement in the side effects ive kind of resigned. sucks because going bald makes me quite depressed and I haven't been able to really resolve that not with therapy, not with meditation, not with focusing on other things, it has a major negative impact on my life. and so I am inclined to just accept the sexual side effects. because really they f*** with my mind but less so than full on Norwood 6 coming in hard at my age.


the thing is all the new stuff is based around anti androgens which makes sense because they actually are the very root of this. so I imagine even a maintenance drug that doesnt cause systemic anti androgenic side effects will be 10 years+ away

 

[badnewsbearer]

like @Modill there is not one actually promising maintenance drug in the pipeline that does not go over the anti androgenic pathway. I have read through a lot of literature and aside from targeting the androgen receptor or androgen production locally, there is really no genuinely interesting approach. with the only exception being amplifica who is only trust worthy bc their researcher plikus actually knows what he is talking about. everything else is complete money grab trash

 

[Min0]

But hairloss feelings? Do you notice anything?

well for now, it stops the itch! too soon to talk results tho, i'm gonna give it time. obviously it's not as strong as pyri that's for sure.

 

[Min0]

i dont understand @Min0 why you would rather spend a large amount of money of fluridil which is very costly and no study supports its effectiveness than investigate how to target the drugs that DO work much more effectively to the skin so a much lower dose can be used an less goes into the circulation.

because money is not a problem for me. and i'm not a biologist to investigate more efficient vehicles.
if the free market hasn't solved the vehicle problem yet, i'm not the one who's gonna come up with a breakthrough on this front obviously.

 

[badnewsbearer]

because money is not a problem for me. and i'm not a biologist to investigate more efficient vehicles.
if the free market hasn't solved the vehicle problem yet, i'm not the one who's gonna come up with a breakthrough on this front obviously.

what aboit natural products thag have anti androgenic properties in multiple steps of the androgen metabolism? thete are some plants that have 5AR inhibiting, AR antagonism or even some like propolis can degrade the androgen receptor like GT. they are even investigated for cancer research. some of tjem might have some different systemic properties. just need to identify them, extract them and prepare them in a solution that penetrates the scalp skin



there is actually a lot of ways and rate limiting steps through which androgen signsling can be disrupted:

-translocation of the androgen receptor bsck into the cytoplasm


- degradation of the AR post transcriptionally

- inhibition of mRNA of the AR

- AR antagonism

- Reducing either expression or activity of 5AR

- codomain biding and prevention of binding of cofactors to the AR so it doesnt get activated

-increase aromatase expression locally

-inhibit testosterone production locally(yes, in favt hair follicles have shown to be able to synthesize their own testosterone locally as well)


-degrade 5AR



plant based products have a bad reputation but thats by they have not been screened properly. in theory if you have something like propolis which is reported to degrade the AR in vitro and have a good vehicle like a nanoparticle lipids and have good delivery of the molecules than it has a high chance of working in vivo.

also there are as ive just said a great many ways to interfer with steroid signaling not just antagonists and 5AR inhibitors