Kintor Pharma Announces Completion of Subject Enrollment and Dosing in Phase I Clinical Trial of AR-PROTAC(GT20029) in the US

Ralph Wiggum

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Suzhou, October 27, 2022 - Kintor Pharmaceutical Limited (“Kintor Pharma”, HKEX: 9939), a clinical-stage biotechnology company developing innovative small molecules and biological therapeutics, today announced that the company has completed the enrollment and dosing of 120 subjects for its U.S. phase I clinical trial of GT20029 for the treatment of androgenetic alopecia (Androgenetic Alopecia) and acne on 25 October 2022.
 

Left4bald

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Nice one ! Another one from Kintor (with pyri)

it's interesting what they said :

" As a PROTAC compound, GT20029 is expected to administer less frequently and more efficient to KX-826, to meet the needs of patients with different types of alopecia and acne. Alopecia affects about 1.6 billion people and acne affects about 0.72 billion people worldwide, with both indications having a huge unmet clinical need. By accelerating the clinical process of GT20029 and KX-826, we hope we can advance new and effective treatment options for patients with Androgenetic Alopecia and acne worldwide.”
 

badnewsbearer

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will this just be another thing from Kintor where they claim no sexual side effects but then eventually these do pop up when people try it? what is the mechanism(for real) preventing this drug from going systemic and causing sexual sides there? it won't be worse(as some people claim) as an anti androgen because even if androgen receptors in for example the penis will be degraded, they will immediately be synthesized again however it won't be much better either. there must be some research on their side to keep this local or some animal study that gives them the idea that it will be?

like what Olix did with their degrader molecule, they at least tested it in a Franz Diffusion cell with human skin to predict its systemic absorption potential. with all of Kintors ventures one thing is missing and that is smart delivery design(or smart drug design really although with the prozac this cant really be said bc its fairly advanced and innovative)


I mean what's the point if this goes just as systemic as pyrilutamide? I am less confident in this project which was very much hyped up a year ago after figuring out that pyrilutamide does have sexual side effects unlike their in house studies suggest.
 

inmyhead

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will this just be another thing from Kintor where they claim no sexual side effects but then eventually these do pop up when people try it? what is the mechanism(for real) preventing this drug from going systemic and causing sexual sides there? it won't be worse(as some people claim) as an anti androgen because even if androgen receptors in for example the penis will be degraded, they will immediately be synthesized again however it won't be much better either. there must be some research on their side to keep this local or some animal study that gives them the idea that it will be?

like what Olix did with their degrader molecule, they at least tested it in a Franz Diffusion cell with human skin to predict its systemic absorption potential. with all of Kintors ventures one thing is missing and that is smart delivery design(or smart drug design really although with the prozac this cant really be said bc its fairly advanced and innovative)


I mean what's the point if this goes just as systemic as pyrilutamide? I am less confident in this project which was very much hyped up a year ago after figuring out that pyrilutamide does have sexual side effects unlike their in house studies suggest.
The drug hasn't even showed efficiency yet and people are already complaining about sexual sides lmao
 

kiwi666

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will this just be another thing from Kintor where they claim no sexual side effects but then eventually these do pop up when people try it? what is the mechanism(for real) preventing this drug from going systemic and causing sexual sides there? it won't be worse(as some people claim) as an anti androgen because even if androgen receptors in for example the penis will be degraded, they will immediately be synthesized again however it won't be much better either. there must be some research on their side to keep this local or some animal study that gives them the idea that it will be?

like what Olix did with their degrader molecule, they at least tested it in a Franz Diffusion cell with human skin to predict its systemic absorption potential. with all of Kintors ventures one thing is missing and that is smart delivery design(or smart drug design really although with the prozac this cant really be said bc its fairly advanced and innovative)


I mean what's the point if this goes just as systemic as pyrilutamide? I am less confident in this project which was very much hyped up a year ago after figuring out that pyrilutamide does have sexual side effects unlike their in house studies suggest.
Whinge whinge whinge maybe your hair loss is stress related
 

Ralph Wiggum

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Kintor Pharma Announced Completion of Phase I Trial of the World’s First PROTAC Compound (GT20029) for Topical Use​


 

badnewsbearer

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i don't know what to think about this. after the realization that pyrilutamide does have systemic side effects not better than finasteride and can cause sexual side effects even though their marketing gig was that it doesnt its hard to be excited about anything from them.

> Following multiple-dose topical administration of GT20029, the mean maximum drug concentrations of all cohorts were lower than 0.05ng/mL.

nobody knows what this means. in pyrilutamide trials they also wrote something like this as if it was some high achievement but there is no reference for these numbers, nobody understands what t means to have 0.05ng/ml of a degrader in your blood.

>The pharmacokinetic results showed that the topical use of PROTAC compound could penetrate into the body, but the exposure was much lower than KX-826 (small molecule antagonist), indicating that the safety was controllable

so you have an androgen receptor degrader going systemic, the safety is "controllable" whatever that means, usually n these report everything is always "excellent" or "very safe" and not tolerable. additionally, the comparison with pyrilutamide here makes no sense as it is a completely different molecule. 1 molecule of GT20029 could degrade 1000 receptors while 1 pyr molecule could only bind to one for all we know and so the concentration in the body is not a comparable metric.


again they will develop the most advanced drug but they cant use a good vehicle to deliver it. so it causes side effects and thats the end of the story. probably developing a better vehicle would cost less in ROD then one single trial run
 

Modill

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i don't know what to think about this. after the realization that pyrilutamide does have systemic side effects not better than finasteride and can cause sexual side effects even though their marketing gig was that it doesnt its hard to be excited about anything from them.

> Following multiple-dose topical administration of GT20029, the mean maximum drug concentrations of all cohorts were lower than 0.05ng/mL.

nobody knows what this means. in pyrilutamide trials they also wrote something like this as if it was some high achievement but there is no reference for these numbers, nobody understands what t means to have 0.05ng/ml of a degrader in your blood.

>The pharmacokinetic results showed that the topical use of PROTAC compound could penetrate into the body, but the exposure was much lower than KX-826 (small molecule antagonist), indicating that the safety was controllable

so you have an androgen receptor degrader going systemic, the safety is "controllable" whatever that means, usually n these report everything is always "excellent" or "very safe" and not tolerable. additionally, the comparison with pyrilutamide here makes no sense as it is a completely different molecule. 1 molecule of GT20029 could degrade 1000 receptors while 1 pyr molecule could only bind to one for all we know and so the concentration in the body is not a comparable metric.


again they will develop the most advanced drug but they cant use a good vehicle to deliver it. so it causes side effects and thats the end of the story. probably developing a better vehicle would cost less in ROD then one single trial run
I'll tell you what this means.

When Kintor said about Pyrilutamide: "there are no sexual side effects", he really meant: "there are sexual side effects". And when he said "there were no deaths", I am beginning to think that what he meant was: "they all died within 6 months".

You can't imagine how my heart was pounding after almost 2 months of use. I had very suspicious discomfort and pain and palpitations.

Anyone would trust this Chinese quack.
 

badnewsbearer

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I'll tell you what this means.

When Kintor said about Pyrilutamide: "there are no sexual side effects", he really meant: "there are sexual side effects". And when he said "there were no deaths", I am beginning to think that what he meant was: "they all died within 6 months".

You can't imagine how my heart was pounding after almost 2 months of use. I had very suspicious discomfort and pain and palpitations.

Anyone would trust this Chinese quack.
yeah but in your case I think its more that you got it from a Chinese lab with lots of impurities than anything else. also by your description it sounds a lot like placebo and lack of understanding of how androgens work. e.g your libido being demolished minutes after applying is just completely unrealistic. I also dont think the end product will cause heart problems because that'd not be a side effect acceptable to western regulators, sexual side effects are classified as mild still which makes sense because they aren't life threatening. heart related problems would be classified different. who knows what you consumed there.
 

Modill

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yeah but in your case I think its more that you got it from a Chinese lab with lots of impurities than anything else. also by your description it sounds a lot like placebo and lack of understanding of how androgens work. e.g your libido being demolished minutes after applying is just completely unrealistic. I also dont think the end product will cause heart problems because that'd not be a side effect acceptable to western regulators, sexual side effects are classified as mild still which makes sense because they aren't life threatening. heart related problems would be classified different. who knows what you consumed there.
- I bought from Actifolic, the Netherlands, like most of the Europeans on this forum who have bought.
- It's not a placebo, how tiresome you are. In fact, I was researching and patients who have prostate cancer and take androgen depletion treatments have a 2-3% chance of heart failure. The effects of administering Pyri were noticed after 30 min.
- So heart problems are not acceptable to western regulators, but total suppression of libido yes? FDA and EFSA is a mafia my friend. Finasteride makes prostate cancer more difficult to detect, can cause breast cancer and lifelong erectile dysfunction, as well as arrhythmias. Everything says it on the prospectus, and even so it is sold without a prescription in pharmacies for an aesthetic problem.
- The FDA has approved the injection of the COVID vaccine to the entire child population, when the child population is not affected by this disease, and when it is known that the vaccine does not prevent the transmission of infection between people. Therefore, if children do not die of Covid, and the vaccine does not prevent transmission, what is the reason for injecting so many children with an experimental vaccine with an unknown and never used technology (RNAm)? Do you think the FDA cares about your health? I bet you all you want that the FDA will approve the use of Pyrilutamide diluted in the same solution as Actifolic and that the package insert will say what Kintor said: no sexual side effects. I'm sure
 

badnewsbearer

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irst I highly doubt they are producing it in a lab in the Netherlands, they probably get it from china and then sell it from there. second, we are talking about androgen deprivation therapy. the goal of androgen deprivation therapy is to rid your body of as many androgenic action as you possibly can. this is incomparable to a small dose of a rather weak anti androgen applied to your head. I mean, we are talking about orders of magnitude worse here. the phase 2 safety trial has not detected any heart related problems.

yes, "total suppression" of libido is an acceptable side effect in many drug classes as it is not considered life threatening and depending on the underlying condition, it is the better choice. (e.g for depression/mental health issues)

then you go on a rant that has long been debunked about the most ludicrous claims about finasteride. there is no evidence to support a connection between prostate cancer and finasteride (it might actually help for treatment) as well as arrhythmias, the connection with breast cancer has been disproven by a bunch of studies as well.
so basically all the side effects of finasteride are rather non severe (which is not the same as non bothersome or life quality impacting, just not deadly) and the other ones(breast cancer) are made up. I am not suggesting these sides are not reason enough to quit, I am just stating that a regulatory body will rank them very different

yes I actually do think despite many problems and possible corruption that the FDA does care about my health. especially when a foreign company is trying to sell their sh*t here. the FDA has the same problems as any other agency, e.g environmental agency etc but on an international standard it is pretty rigorous and heart related side effects with a drug used for aesthetics is not going to be acceptable no matter how much you make up about finasteride or the covid vaccines

>will say what Kintor said: no sexual side effects. I'm sure

they will write what the result of the phase 3 trials will be. the FDA will review the methology used. that is the appropriate process. at this point you are the one using a research chemical and complaining about sides a few minutes after application, that is considered the lowest form of evidence in medicine that can exist while a multi stage RCT is the highest form of evidence. also finasteride had it on the label too. generally everything that can happen will be on the label no matter how small the chance
 

Modill

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OK, so you are still confident that the results of the Kinton study are true. You believe what they claim as far as I can see. Well look buddy, the blood Pyri levels in the study are higher than most people's DHT levels. If pyri has such a high affinity for the receptor, isn't that total androgen deprivation? In my view, yes.

And as for total libido suppression, who is talking about life saving treatments? I am talking about an aesthetic problem: baldness.

On the other hand, I see that you are one of those who think finasteride is not that serious. Great, with that you have said it all. You don't believe what it says on the finasteride package insert either. I repeat it again because I did not say that finasteride causes cancer, I said that finasteride can hinder the detection of cancer. But while we are at it I also tell you: finasteride causes an increase in estradiol because testosterone does not convert to DHT and passes all of it to estradiol, and that CAN cause prostate cancer.

What is the problem of noticing side effects after 30 min? The scalp is super irrigated. Take a cocaine shred, you won't have to wait even 5 min to enjoy its effects.
 

badnewsbearer

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"Finasteride makes prostate cancer more difficult to detect, can cause breast cancer"

the scalp is vascular but it is simply not enough time to penetrate and affect protein biosynthesis at the corresponding receptor. and in that quantity too. yeah, finasteride causes a 15% increase in estradiol (some studies report no increase at all) but in return it lowers prostate DHT by 90% and DHT is much more relevant for prostate cancer than estradiol so you could make the argument the other way around that finasteride is good against prostate cancer. it is an anti androgen after all. why do you think they use anti androgens for prostate cancer, they too increase Estradiol(if its just an antagonist in contrast to gonad hormone blockers)

i do not know if their study results are true but I think it is ridiculous to assume they aren't when the reference is a bunch of people on online forums who ordered the drug online from an underground lab. if we stop valuing scientific methods then why have a discussion anymore at all? okay, they lie just as they wish, the FDA is an evil organization that will approve anything and applying a tiny dose of an anti androgen to the scalp(which is much thicker than other skin areas) is comparable to taking cocaine (which is completely ridiculous because cocaine does NOT work by modulating protein synthesis, thats the entire point, thats why it takes much longer)


I believe finasteride is a sh*t drug completely inappropriate to use for hair loss but sadly it works very well so there has been no alternative so far. not because of evil conspiracies but because the market is already saturated because finasteride works for many and is well tolerated, that is not my personal opinion as someone who did have significant side effects but the opinion of numerous clinical studies which I believe in, again because despite poor mythology in some of them the quality of evidence is still a lot better than people on an online forum


>And as for total libido suppression, who is talking about life saving treatments? I am talking about an aesthetic problem: baldness.

this does not matter. in a free country, a drug that is save as in does not cause death or severe disease should be approved and everyone can decide for themselves if it is worth to take it or not. the reward is lower(treating baldness is less rewarding than treating cancer) but the risk is also lower(low libido s a lot less of an issue as seizures etc like som drugs have). thats why it can be justified to approve.

after all, smoking is "approved", all kinds of trashy food is approved, doing these things serves no greater purpose but you can do what you want so why shouldn't you not be able to treat hair loss at your own risk.


also as far as the studies go, if we assume pyrilutamide as safety profile like finasteride, then the sample size was too little to detect all potential causes of dysfunction. a larger sample size is needed to have clearance on that. thats what a phase 3 is for. so right now I will say, I dont think its side effect free and that will show in phase 3. I dont think they are actively suppressing side effects because that won't work in the US
 

badnewsbearer

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posting this here because it is research on topical intrafollicular deliver from this year and I think it could be very relevant for the receptor degrader:



so I think GT20029 could be the cure. but I think people need to understand that Kintor is a company with not a lot of competency in DERMATOLOGY so they will try to deliver the protac degrader with a basic vehicle from 1995 ethanol pg just like they do with pyrilutamide. recent research has beens per promising using charged nano carriers. basically there is three pathways how a drug can enter the body topically.

1) intracellular
2) intercellular
3)interfollicular

https://www.mdpi.com/pharmaceutics/...ml/images/pharmaceutics-14-00286-g002-550.jpg



conventional vehicles either go directly through the cells or between the membranes. so if you apply pyrilutamide or finasteride or GT for that matter it goes through the skin cells and eventually hits either an artery or it goes deeper into the tissue where it hits blood circulation. it does not go into the dermal papilla very much and it causes sides by going systemic. the vehicle can influence which pathway is preferred(see table 3 of the paper below)



if you have a different carrier it can be made to prefer the inter follicular pathway. hairs are full of lipids, lipids have a certain charge and this can be used to force a drug down the hair shaft right into the follicle. this allows usage of concentrations far far far lower than before and with a more targeted delivery. this is also the idea behind liposomal and nano carriers.

however many things influence how well this works for example the excipients(in the paper below there is a table showing which ingredients lead to preference of which pathway), the charge of the particles, particle size etc etc. even scalp hydration through the vehicle too.

for anybody interested in this, here is a paper from 2022 describing this idea

https://www.mdpi.com/1999-4923/14/2/286/htm#B40-pharmaceutics-14-00286 (

Nanostructured Drug Delivery Systems for Targeting 5-α-Reductase Inhibitors to the Hair Follicle)​


this is about targeting 5AR but this can work for RU, CB, pyrilutamide, basically even minoxidil can be delivered this way. I read a study that showed 10 fold increase in minoxidil concentration in the hair bulb with a nano carrier. I think this can be really powerful if you encapsulate the protac degrader in it

2023 is not the time people should be using stupid ethanol and pg solutions. it will just straight go into the blood. however despite research there is no real commercial product yet. I talked to a pharmacist and he said this field is growing now, better delivery mechanisms are being researched.


if we can get something like GT20029 formulated in such a vehicle, maybe in combination with pyrilutamide or something, we can use doses 5-10 times less than before and target them right into the dermal papilla so less drug in the blood, more where it needs to go. imagine building up a reservoir of the protac degrader right in the hair follicle that lasts for many days or weeks. you could dose it very small and probably avoid systemic sides. I think this could be super exciting

in my opinion this is the most promising, certainly more so than hair cloning. delivering an anti androgen and an androgen receptor degrader right down the hair shaft into the follicle. and it is actually very feasible. making these things is not super complicated but you need expertise and equipment, basically you need a good compounding pharmacist that is up for doing this. there are many papers from 2019/20/21 so its an active field and can be referenced by them
 
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