Kintor Releases Phase 2 Trial Results for GT20029
Kintor Pharmaceuticals has announced that its proteolysis targeting chimera (PROTAC) drug GT20029 has reached its primary endpoint in its Phase 2 trial in China. GT20029 is a topical PROTAC targeted toward AGA.
What are PROTACs?
PROTACs are a novel class of heterobifunctional molecules that can induce the degradation of target proteins by hijacking the cell’s ubiquitin-proteasome system. The key features of PROTACs are:
- They are composed of two parts – a ligand that binds to the target protein of interest and a ligand that binds to an E3 ubiquitin ligase enzyme
- The PROTAC brings the protein of interest and E3 ligase into proximity, allowing the ligase to ubiquitinate the protein of interest and mark it for degradation.
- This process results in the rapid and selective depletion of the target protein rather than just inhibiting its activity like traditional small molecule drugs.
PROTACs offer several advantages over traditional approaches, including targeting “undruggable” proteins that lack well-defined binding pockets and the potential for a more durable pharmacological effect. PROTACs can be designed using either small molecule or peptide ligands to bind the protein of interest and E3 ligase, leading to different categories like bioPROTACs and hybrid PROTACs.
What is GT20029?
GT20029 is a PROTAC that targets androgen receptor (AR) proteins for degradation. The PROTAC platform used in GT20029 consists of three components: a recruiting element that binds to the AR protein, an E3 ubiquitin ligase recruiting element, and a linker that connects the two. When these three come together, the process of ubiquitination effectively breaks down and degrades the protein. By degrading the AR, GT20029 can block the AR pathway, which may prevent hair follicle miniaturization and hair thinning.
What Other Drugs Target Androgen Receptors?
There are a variety of other treatments out there that also target androgens but in different ways.
Anti-Androgen Treatments
- Pyrilutamide is a non-steroidal anti-androgen (NSAA) that blocks testosterone and DHT from binding to the AR. It does this by binding to AR receptors in the hair follicles, which prevents the effects of androgens on hair follicle miniaturization.
- CB-03-01 is a steroidal anti-androgen, that works similarly to pyrilutamide. It also binds to the AR in the skin, competing with the binding of androgens like DHT.
- CosmeRNA utilizes short interfering RNA (siRNA). siRNA interferes with protein production from mRNA, which, in this case, is an androgen receptor. In CosmeRNA, the siRNA is called siRNA-AR 68. . Because it is a topical treatment, it is believed to interfere only with androgen receptor production in the specific area of the scalp to which it is applied, minimizing systemic effects associated with other AGA treatments.
Phase 2 Trial Results
This double-blind, placebo-controlled study was designed to determine the efficacy and safety of GT20029 for treating male androgenic alopecia (AGA) and the recommended dosage for a Phase 3 trial.
Details and results of the completed trial are as follows (as reported through a press release):
- The study included 180 male patients with AGA.
- The patients were split into once-daily (“QD”) or twice-weekly (“BIW”) groups, each with its control (placebo) or dosing (0.5%/1%) group.
- Mean non-vellus target area hair count (TAHC) was measured at baseline and endline.
- The 0.5% “QD” GT20029 group showed an increase of 16.8 hairs/cm2 (an increase of 6.69 hairs/cm2 over the placebo), which was a statistically significant increase (P <0.05).
- The 1% “BIW” GT20029 group showed an increase of 11.94 hairs/cm2 (an increase of 7.36 hairs/cm2 over the placebo), which was a statistically significant increase (P<0.05).
- The topical treatment showed good safety and tolerability, with adverse events comparable to the placebo.
- Kintor has identified the 1% “BIW” dosage as the optimal dose for its Phase 3 trial in China.
Reflections
We have previously mentioned GT20029 here. While it is always encouraging to see novel treatments for AGA progress through trials and with statistically significant results, there are always questions to be answered:
1. How does this treatment stand up to existing treatments for AGA? While the results show statistically significant improvements over the placebo, it would be helpful to understand how GT20029 performs relative to the current standard of care.
2. What is the distribution of TAHC across participants in the groups? Although the results were positive, with an overall statistically significant outcome, we don’t know if these results are due to a small number of “hyper responders” or if average participants’ responses drove the results.
We look forward to seeing the results of this trial in a peer-reviewed journal.
Do you think there are any other unanswered questions from this press release? Let us know in the comments.
Very encouraging results given this was just a 12 week study. But excellent point that we need to exclude these seemingly very positive results are not skewed due to hyper responders. And see the results at 24 weeks.
I think if this product came to market, twice weekly topical application would be a very welcome dosing regime, and would help massively with compliance, something that topicals which require daily, or twice daily applications, may suffer from.
From my point of view, this biggest question surrounding GT20029, is that of safety. Whilst PROTACs which target the AR sound very beneficial in the scalp, it’s certainly something I think most males would be very wary about going systemic to any great degree. The study does mention specifically there were no sexual side effects and seemingly no major side effects, so this is encouraging. It would be nice to know if they measured plasma/serum levels of GT20029 and it’s metabolites if it has any. Indeed it would just be reassuring to know a little more about its pharmacokinetics. Admin do you have information about this sort of data? Eg half-life, route of elimination from the body or if they have ever measured serum levels prior? I’m struggling to find this info. I know they measured serum levels for pyrilutamide in phase 2.
Bottom line the outcome data on safety seems good here which is very reassuring. If a larger and longer phase 3 study backs this up, and GT20029 does indeed seem to stay local to the scalp and only really affect AR there, then this is the future drug I am most excited about and eager to try when it (hopefully) comes out.
Thanks for the update Admin.
Biw means twice a week not 2x daily
You’re absolutely right, have corrected the article to reflect that!
Hi Ray. Yes I am aware. I just meant any topical with a twice daily application can be a hassle to some, such as minoxidil or (in the future) CB. Any topical with a reduced application frequency is a win in my eyes.
Hi
Is it twice daily or weekly?
Weekly! I have updated the article to reflect that.
I’m not an expert and I don’t know
Many people on various forums are talking
That the difference between CosmeRNA and GT20029 is very small
Hello Admin. Can you please update the pipeline overview of all companies? I believe the last update was more than a year ago. (april 2023) For example, Technoderma has completed their phase 2a trial. (24.3 hairs/cm2)
This page has been fairly quiet so far this year, rarely any updates. No new companies on the horizon or existing company updates? Whatever happened to Eirion therapeutics? They burst on the scene 3 years ago and nothing at all since not even a mention of clinical trials. Near half way through 2024 and I’m starting to lose all hope
VDPHL appears to just be oral minoxidil. Haven’t seen this news elsewhere yet
Veradermics just published a patent for an oral minoxidil formulation: https://www.lens.org/lens/patent/075-725-786-620-163/frontpage?l=en
Wow, that’s really unfortunate. How could they patent someone that’s already available…
You’re right, and the patent application’s current status is that it’s *not* been granted. This is in part due to prior art for an modified release formulation of minoxidil in a Follica patent.
It was also denied by the patent reviewer for other listed reasons, mainly that they did not believe enough support was present in the application for this to represents a novel invention. I think this blocker will be easy for Veradermics to overcome with the clinical data they’ve already collected or are in the process of collecting.
They now appear to be recruiting for their phase II trial: https://www.reddit.com/r/HairlossResearch/comments/1ckmg1b/comment/l2q4vz3/
It’s disappointing that it’s only a sustained release minoxidil, but since the remaining concerns about OM are mostly about cardiac and blood-pressure side effects, anything they learn and reveal has immense safety value to the growing number of patients using it.
Veradermics may not have expected the denial of the patent grant, since they had previously stated they wanted to come out of stealth mode for this product ASAP, and doing that got pushed back until summer at least. Nothing indicates that they’ve given up.
link to Veradermics CEO LinkedIn post with AGA recruitment survey (phase 2?): https://www.linkedin.com/posts/veradermics_activity-7170876796467400704-TrL6
direct link to survey: https://www.surveymonkey.com/r/4HAIRLOSS
“Androgenetic Alopecia (Hair Loss) Pre-qualification Questionnaire” title rules out this being for their alopecia areata pipeline drug (VDAA)
It is incredible that they have maintained so much confidentiality for a drug that is already widely prescribed. Well, what a disappointment… I also don’t understand why a drug with proven efficacy and quite safe has to be prescribed off-label. The FDA is crap.
the pace of development has never been slower. there’s literally nothing close to fixing balding. the timelines have all been pushed back. Stemson is probably a 2030s thing now. Just ridiculous.
I don’t know if this will provide some type of relief for you baldasian, but Pelage is moving onto their second phase approximately next month and their regenerative medicine has insane potential and they are in fact moving at a good pace through these trials. Amplifica should also be releasing their data in the coming weeks. I believe Yokohoma is planning on bringing their hair multiplication in the next couple of years, and Japan don’t have long tedious trials compared to the US.
Baldasian, you are spot on. The cure is always 3 years away. 3 years pass and nothing. Then they say it will be another 3 years. 😞 Just get a good hairpiece and fagedda bout it.
Another Trial … Kintor is not giving up.
https://www.marketscreener.com/quote/stock/KINTOR-PHARMACEUTICAL-LIM-111325374/news/Kintor-Pharmaceutical-Limited-Announces-That-the-Clinical-Trial-of-Its-In-House-Developed-and-Potent-46817606/
KX-826 has received the INCI Designation. INCI names are systemic names recognised worldwide for the identification of cosmetic ingredients and are cited by product labelling regulations in many countries. The assignation would facilitate the global launch of the company’s functional cosmetics with KX-826 (likely 0.5%) as the main ingredient.
Business as usual for these companies,eg,false hope,failure after failure and the ever moving 5-10 year time frame for a solution.
It’s a joke.