Aclaris / Jak / Androgenetic Alopecia - How Optimistic Are We?

[paleocapa89]

I couldn't find an official JAK thread so I created one. To my interpretation, there definitely something is going on here..

"Aclaris Therapeutics (ACRS) Granted 2 Patents Allowance Applications for Baricitnib and Decernotinib
April 4, 2017 8:04 AM
Aclaris Therapeutics, Inc. (NASDAQ: ACRS) today announced that Columbia University has received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for two patent applications covering methods related to the use and administration of baricitinib (LY3009104) and decernotinib (VX-509), respectively, for the treatment of hair loss disorders and for inducing hair growth. These newly allowed patent applications are owned by The Trustees of Columbia University in the City of New York and exclusively licensed to Aclaris Therapeutics, Inc. These patent applications are the latest U.S. applications to be allowed in connection with Aclaris' janus kinase inhibitor (JAK) drug development program for hair loss disorders. A separate Columbia patent covering the use of ruxolitinib for the treatment of hair loss disorders and for inducing hair growth was issued in the U.S. in December 2015.

“We are extremely pleased with this expansion of the patent portfolio we exclusively licensed from Columbia. These allowances expand the breadth of and further validate our JAK inhibitor intellectual property portfolio covering methods of use for certain JAK inhibitors for the treatment of hair loss disorders. The allowance of these patent applications is another step towards the development of a robust portfolio relating to JAK inhibition and hair loss,” said Dr. Neal Walker, President and Chief Executive Officer of Aclaris.

The claims of these newly allowed patent applications cover methods of inducing hair growth and treating various hair loss disorders, including alopecia areata and androgenetic alopecia, by administering baricitinib or decernotinib, respectively. Additional allowed claims pertain to methods of using baricitinib or decernotinib to treat other hair loss disorders, as well as to treat particular phenotypes of alopecia areata.

Aclaris has exclusively licensed several patents and patent applications involving novel selective JAK 1/3 inhibitors, including a patent portfolio from Rigel Pharmaceuticals, Inc. that covers ATI-50001 as well as ATI-50002, a topical formulation also being developed as a potential treatment for alopecia areata. In addition, Aclaris has exclusively licensed a patent portfolio from JAKPharm and Key Organics directed to novel covalently binding, highly selective JAK 3 inhibitors. Finally, Aclaris has exclusively licensed a patent portfolio from Columbia University directed to methods of using JAK inhibitors for the treatment of alopecia areata, androgenetic alopecia, and other dermatological conditions. This portfolio includes the recently allowed U.S. applications discussed above, a recently issued U.S. patent directed to methods of treating alopecia areata, androgenetic alopecia and other hair loss disorders by administering ruxolitinib, and a recently issued patent in Japan directed to pharmaceutical compositions comprising ruxolitinib, baricitinib or other JAK inhibitors for use in treating alopecia areata, androgenetic alopecia and other hair loss disorders.
"

source: https://www.streetinsider.com/dr/news.php?id=12740699&gfv=1
and HLC2020 comment.

 

[Xander94]

Well in the next 5-10 years....

 

[paleocapa89]

I think some of these drugs are already approved and/or in advanced stages of testing.

 

[Royaume]

Sounds very interesting. Who else thinks that it seems that they know that these JAK inhibitors work for Androgenetic Alopecia?
They know something but they don't want to share the information.... hmmmmm

 

[paleocapa89]

Yes, I hope so. I remember maybe a year ago Angela Christiano was talking about covalently binding, highly selective JAK inhibitors might be needed to work for Androgenetic Alopecia and now they bought a portfolio of those patents...

To me it seems like they may feel they are onto something with this JAK pathway so they bought a shitload of those patents and will be trialing them.

 

[Royaume]

Press Releases
Aclaris Therapeutics Hosts Symposium on JAK Inhibitors at the 76th Annual Society for Investigative Dermatology Meeting

http://phx.corporate-ir.net/phoenix.zhtml?c=254196&p=irol-newsArticle_Print&ID=2263953

unfortunately they will not talk about andrigenetic alopecia. Maybe during the question and answer session?


What do the others think about JAK inhibitors? It's very interesting topic but it's interesting that there aren't many thoughts on this.

 

[baldingAF]

I think it's really worth investigating. Not only Aclaris but Follica was also mentioning JAK inhibitors and tyrosine kinase inhibitors in their patent, could be the hype from 2015 or could not be. Even then many studies that show even a small amount of regrowth mention the JAK/STAT pathway being affected in some regard.....Damn wouldn't it be nice if it worked for us like it did areata

 

[Royaume]

I think it's really worth investigating. Not only Aclaris but Follica was also mentioning JAK inhibitors and tyrosine kinase inhibitors in their patent, could be the hype from 2015 or could not be. Even then many studies that show even a small amount of regrowth mention the JAK/STAT pathway being affected in some regard.....Damn wouldn't it be nice if it worked for us like it did areata

I think that aclaris knows that it works. Even Dr. Neal Walker himself said that jak inhibitor do have an effect on Androgenetic Alopecia as they are inducing hair growth. Let's see what happens, who knows? maybe it has a similar effect like areata.

Don't forget what Brotzu said. All kinds of alopecias have a problem with blood flow (?? cannot remember what he exactly said but it was something about the blow flow)

 

[Royaume]

Conditional ablation of JAK-STAT5 signaling induces anagen hair growth
E Wang1 and AM Christiano2 1 Columbia University, New York City, NY and 2 Columbia University, New York, NY
We have previously shown that pharmacological inhibition of the JAK-STAT pathway using small molecule inhibitors during murine telogen can rapidly initiate anagen, suggesting the
presence of an inhibitory factor that promotes quiescence in hair follicle stem cells (HFSCs) via this pathway. We have also shown that JAK-STAT3 and JAK-STAT5 pathways are prefer-entially and dynamically expressed in the HFSCs during murine telogen. To test the hy-
pothesis that JAK-STAT signaling promotes hair growth, we used STAT5 floxed mice, together with two different inducible CreER drivers targeting the hair follicle (K5-CreERT2, K14-
CreER). We showed that systemic tamoxifen treatment during mid-telogen (P60) for 4 days is sufficient to knock-out STAT5 expression in the epidermal compartment. Hair growth was
initiated in the shaved telogen skin of K5-CreERT2 :: STAT5fl/fl and K14-CreER :: STAT5fl/fl mice after 3 weeks of tamoxifen treatment, and not in their wild-type littermates. Moreover,
the new coat of hair in both knockouts grows in uniformly across the dorsum of the mice, in contrast to the patchy or wave-like pattern of spontaneous anagen seen in their wild-type littermates, consistent with an effect due to global genetic induction. Immunofluorescence studies localized pSTAT5 to the bulge region of the hair follicle during telogen, and this
expression peaks at mid-telogen and disappears during the telogen-to-anagen transition. These observations support a dynamic regulation of JAK-STAT5 inhibition and activation throughout telogen, and provide genetic evidence for our previous work showing induction of
anagen hair growth using small molecule JAK inhibitors

Source : Journal of Investigative Dermatology (76th Annual meeting April 26-29 2017)

 

[baldingAF]

You know we can openly buy decernotinib online. It's quite unsafe to use such medication on yourself with dmso or time other topical.... but it's here technically

 

[InBeforeTheCure]

I think it's really worth investigating. Not only Aclaris but Follica was also mentioning JAK inhibitors and tyrosine kinase inhibitors in their patent, could be the hype from 2015 or could not be.

The tyrosine kinase inhibitors the Follica patent refers to are inhibitors of the EGFR (Epidermal Growth Factor Receptor) family of receptor tyrosine kinases. They didn't mention JAK inhibitors.

By “small molecule EGFR inhibitor” is meant a molecule that inhibits the function of one or more EGFR family tyrosine kinases. Tyrosine kinases of the EGFR family include EGFR, HER-2, and HER-4 (see Raymond et al., Drugs 60(Suppl. 1):15 (2000); and Harari et al., Oncogene 19:6102 (2000)). Small molecule EGFR inhibitors include, for example, gefitinib (Baselga et al., Drugs 60(Suppl. 1):33 (2000)), erlotinib (Pollack et al., J. Pharm. Exp. Ther. 291:739 (1999)), lapatinib (Lackey et al., 92nd AACR Meeting, New Orleans, abstract 4582 (2001)), canertinib (Bridges et al., Curr. Med. Chem. 6:825 (1999)), vandetanib (Wedge et al., Cancer Res. 62:4645 (2002)), CL-387785 (Discafani et al., Biochem. Pharmacol. 57:917 (1999)), PKI166 (Takada et al., Drug Metab. Dispos. 32:1272 (2004)), pelitinib (Torrance et al., Nature Medicine 6:1024 (2000)), HKI-272, HKI-357 (for HKI-272 and HKI-357 see, for example, Greenberger et al., 11th NCI-EORTC-AACR Symposium on New Drugs in Cancer Therapy, Amsterdam, abstract 388 (2000); Rabindran et al., Cancer Res. 64:3958 (2004); Holbro et al., Ann. Rev. Pharm. Tox. 44:195 (2004); Tsou et al., J. Med. Chem. 48:1107 (2005); and Tejpar et al., J. Clin. Oncol. ASCO Annual Meeting Proc. 22:3579 (2004)), and leflunomide (Kochhar et al., FEBS Lett. 334:161 (1993)). The structures for each of these compounds is provided below in Table 1.

https://www.google.com/patents/US8252749

 

[Cody1212]

You know we can openly buy decernotinib online. It's quite unsafe to use such medication on yourself with dmso or time other topical.... but it's here technically

It looks like we can buy it and it's not that expensive...is this stuff dangerous as hell?

 

[baldingAF]

@zaman can you give me a link to those testimonials or just an account of yours- solution numbers n what not.

@Cody1212 just look it up online and check out the sides.... pretty scary ish.

People at HLC2020 are really excited about JAK inhibitors. In the comments you see em going Gaga for a topical JAK.....

 

[Cody1212]

Crazy weird sides...not bro science sh*t. Sounds like people have died from this sh*t.

 

[baldingAF]

Berberine Chloride

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171864/

 

[baldingAF]

Can anyone link me to where people on sites tried JAK inhibs for themselves in their own manner. Wana read those reports and see how that went down. I know no one got anything but I'd like to see the mechanism and what not if I could get some help

 

[Balding curse]

I remember someone on BTT was talking about his experience with JAK inhibitors, he was taking the pills, for one month I guess to treat male pattern baldness, and he said that he didn't see any result, he said it's very expensive and risky.

 

[baldingAF]

I remember someone on BTT was talking about his experience with JAK inhibitors, he was taking the pills, for one month I guess to treat male pattern baldness, and he said that he didn't see any result, he said it's very expensive and risky.

Topical is, more times then not, great because it reduces side effects as its applied, concentrated in one area. So far all these studies that were done in vivo as well as interviews all point to topicals being used. The patent filed by Christiano in 2013 went up as far as 8% solution of JAK inhibitor (+- 1%) and they used it in DMSO solution. I wouldn't go higher than 3% of the newly acquired selective JAK 3 inhibitor DECERNOTINIB which would be about 3mg/100mL of DMSO. It is costly (a 3 month treatment is over 1k) but the more i read into it the more I feel like JAK inhibitors can make a difference but if this goes systemic then you're f**ked.

 

[Balding curse]

Topical is, more times then not, great because it reduces side effects as its applied, concentrated in one area. So far all these studies that were done in vivo as well as interviews all point to topicals being used. The patent filed by Christiano in 2013 went up as far as 8% solution of JAK inhibitor (+- 1%) and they used it in DMSO solution. I wouldn't go higher than 3% of the newly acquired selective JAK 3 inhibitor DECERNOTINIB which would be about 3mg/100mL of DMSO. It is costly (a 3 month treatment is over 1k) but the more i read into it the more I feel like JAK inhibitors can make a difference but if this goes systemic then you're f**ked.

I never heard of someone on fourms is using topical JAK, I would try it if I can afford for it, but over 1k in 3 month probably will f*** me more than JAK side effects

 

[Dench57]

I've tried topical Tofacitinib

doesn't do sh*t