Aclaris Therapeutics and Mechanism of Action

March 2019

In March of 2019, Dr. Angela Christiano’s Columbia University based lab’s Twitter account posted the following:

Etienne Wang's Thesis

In recent years, the Christiano-led Columbia team have published a number of important papers related to JAK inhibitors, JAK-STAT signaling and hair growth. Since I have covered their work many times on this blog, I did not pay much attention to this latest paper. I was also not too keen to yet again research dry subjects such as TREM2+ dermal macrophages, oncostatin and JAK-STAT5 activation.

I am also a bit wary of covering JAK inhibitors too often. Largely due to the slow pace of progress in JAK inhibitor trials for androgenetic alopecia, led by US-based Aclaris Therapeutics. Moreover, technical posts on scientific research papers are not well received by most readers except for the most scientifically minded ones.

May 2019

Aclaris JAK Inhibitor Mechanism of Action

In May of 2019, I outreached to Aclaris Therapeutics to ask them about the progress in their JAK inhibitor trials for male pattern hair loss. In the past, they never replied. However, this time, one of their vice presidents got back to me immediately with the following response:

“Stay tuned. Data in May/June. New MOA postulated In attached paper.”

MOA means “Mechanism of Action”.

Lo and behold, the Aclaris VP had attached the previously discussed Ettiene Wang et. al’s full thesis paper titled:

“A Subset of TREM2+ Dermal Macrophages Secretes Oncostatin M to Maintain Hair Follicle Stem Cell Quiescence and Inhibit Hair Growth.”

June 2019

Last week, Aclaris Therapeutics’s CEO Dr. Neal Walker presented at the annual Jefferies 2019 Healthcare Conference in New York. I used to cover these presentations regularly. The full presentation can be found here.

On page 28, they discuss a new mechanism of action in understanding how JAK inhibitors could help patients with androgenetic alopecia (AGA). In brief, the administration of a JAK inhibitor will turn STAT5 to the OFF position. This in turn promotes hair follicle stem cell activation, and subsequent hair growth.

For some reason, the Aclaris PowerPoint slide’s reference is to Dalessandri, T and Kasper, M., who in turn refer to the Wang paper I discussed earlier.

“TREMendous Macrophages Inhibit Hair Growth”.

Aclaris Topical ATI-50002 JAK Inhibitor Trials

According to the Aclaris vice president who emailed me in May:

The 6-month results from the Phase 2 open-label 31-patient ATI-50002 clinical trial will be finalized during the second quarter of 2019. 12-month data are expected in the fourth quarter of 2019. If the results from this trial are positive, Aclaris expects to initiate an additional Phase 2 trial in the first half of 2020. Note that they sometimes refer to ATI-50002 as ATI-502.

The above information was essentially confirmed in the latest June Aclaris Investor Presentation audio. Best case scenario is that Phase 3 trials will start in 2020.

46 thoughts on “Aclaris Therapeutics and Mechanism of Action”

  1. Your on it admin

    We all want NASA to be right about imminent release but phase2B 2020 means release could be 2022 at best.

    I’ll be in Kobe before then lol

    1. @Egghead I think many people might be as well. The industry is coming to a fork in the road – cell based therapies and everyday topicals / orals. Some people will gravitate more toward permanent solutions and others will stick to the everyday day. “If either works, then why spend all the money?” – I think a lot of people have this mentality. Personally, I would go for a permanent solution. Don’t mind spending a lot for something that’ll actually work.

      Btw, have you seen that video of Shiseido marketing their new facility at a conference? It’s not a very high quality video but the images of the building are the same as the ones at the top of their page. Lmk

    2. Couldn’t agree more. Am fed up with waiting for pills and potions. That said, I assume that as and when cloning starts in Japan it will only be for people resident there so can be monitored?? My hope is that cloning or bio engineering is available in Europe soon as there are at least two companies here who are also working on it. But if Tsuji starts in Japan next year , there will be real hope at last.

      1. @Alan J I don’t think cloning in Japan will be regional. Most of the market is overseas in the US, EU, and other parts of the world. I messaged Shiseido about RCH-01 and they responded it will be available to anyone who comes to Japan and pays for it; I assume it’ll be the same scenario for Tsuji.

        HairClone is a company in Europe doing cloning but they’re preclinical. Tsuji and Shiseido might even offer their treatments in the US / EU by the time HairClone releases. Looks like Shiseido will be released first. Their phase II results release in less than a month.

        1. I’d understood from an interview with HairClone on Follicle Thought that they are planning cell based rejuvenation on a similar timescale to Shiseido. I await with interest Shisedo’s results on this. That said, I really want full regeneration (i.e. true cloning) as I expect that will be the real “cure”. I understood from the same interview that HairClone is working on this as well, though looks as if Tsuji will launch first. I know nothing about Japanese patent law, though hopefully the Tsuji breakthroughs can be licensed in the EU and US (??). Can’t come soon enough for me as after 34 years of very slow balding I am beginning to run out of road (!)

          1. @Alan J Tsuji will probably be liscended in US and EU but after a few years of release thanks to the the FDA but the global market is far greater than the Japanese market so I wouldn’t be surprised. 34 years is a long time to be waiting for something. I only started losing my hair 3 ish years ago but I’m still a teen and genetically speaking I’ll be bald in my early 20s. But with these procedures that won’t happen.

            1. It sure is a long time. I’m 58 now and started losing hair at the back when I was 24. In one respect I have been lucky as although the back went quite quickly the top and front have held on. But they are now so thin that rapidly changing my appearance. Easier to accept when you are in your late 50s than when young, but it is still something that affects my confidence and that I want to fix (not least as I don’t suit it as some men do). Fortunately I can pay and now have the time. The big difference from when I was 24 is that I think we at last have real hope of a permanent cure on the near horizon (I was one of the first to try minoxidil: to no effect). Thank God for science and a globalized World. People have been praying for their hair to grow back and trying quack remedies as long as human history. But only science can and will deliver us. Best wishes

              1. @Alan J I hear you man. And science has made some great leaps and will continue to do so. Hair is just the beginning for his industry. Cell programming is going to advance into more complex organ regeneration like hearts and lungs and bones and livers…For hair though, there isn’t much of a need to hope. It’s just a matter of time in the mid June of 2019.

                Glad you can pay for all that stuff. A large part of the community won’t be able to or won’t want to at first – which is why all these emerging topicals are so popular. Fortunately, I have the funds as well but I definitely have sympathy for those who don’t. But as you said, it’s a globalized world and with all the demand prices will surely drop in the following years after the release of hair cloning procedures.

  2. Admin, when you say ” Largely due to the slow pace of progress in JAK inhibitor trials for androgenetic alopecia, led by US-based Aclaris Therapeutics” do you really feel that this trail is moving any slower than most all other trials? I’m not defending Aclaris however all seem to move at a snails pace, maybe for good reason and maybe not. I can’t name a trial that seems to be progressing more rapidly, can you?

    1. Hi Yoda, JAKs were deemed to “maybe” work for AGA in 2014. And Aclaris has been in the news since 2015. Yet we are still hoping that Phase 2b is done by 2020! Japanese laws may perhaps change these timelines in the US too in future.

      Also, it seems like Aclaris has moved a little faster in the AA trials? For AGA, they still list it as Phase 2 (exploratory).

      1. Admin, what do you believe is going to be the most anticipated / effective topical coming to market? Breezula, Aclaris, or something else? And how would you contrast it to what you believe is the most anticipated cell therapy coming out?

          1. Admin, in your poll you mention a CRISPR/gene modification option. Gene therapy? That’s probably many more years out. It already exists for other conditions but one treatment is like a million dollars. Has there been any updates on that or is it still way too early to tell?

      2. Its a complete joke how long these companies take to do trials. Donald Trump surely wont want to be beaten by Japan for a hairloss cure!

      3. Thanks for the elaboration Admin, to me it seems like all the trials, Histogen, Replicel, Suamed, Follica, etc., etc. move equally slow if not slower. Not whining, just a fact of life.

  3. I think delay in trials come because the human hair cycle is very long (anagen is 3-5 years) so of course the trials must last a while to prove it works

    I am pretty confident it will push hairs to anagen phase, they have also previously proved that the special topical formulation can successfully pierce the human skin and work as intended, this was shown in one of the AA trials from memory.

    My question is will it overpower whatever caused the hairs to be stuck in the telegen phase in the first place. The data will tell us that, here is hoping.

  4. WE ARE LOOKING AT AN IMMINENT RELEASE OF ACLARIS RESULTS BY THIS SUMMER.

    I still think Aclaris has a decent shot at solving this and remember their test subjects were VERY bald thus maybe it just takes years to get back the full head of hair.

    I am hoping.

    1. @Bekoo I see. Aclaris does seem promising, though. They were working with some really bald people. I think they’re going to do well. Please don’t be depressed. All this is coming to an end shortly. It’s not worth your sadness.

  5. Admin, In my opinion Aclaris keeps trials for AGA “slow moving” only to avoid diverting investors’ attention from AA trials which are at a very advanced stage and thus avoiding a marketing cannibalisation effect.

    My gut feeling and sense of logic tells me that Aclaris know very well by now whether Jak Inhibitors trigger hair growth or not. Since they are secretive to a certain extent, I ought to speculate that their trails could prove to be a positive game changer for the global hairloss community.

    Let’s keep a dose of caution, but as I used to state on this blog last year, these are very interesting times.

    I also suggest all followers and commentators to view Aclaris’s latest slideshow and read the lines related to Aga, for there might be just a few notes concerning AGA, but the content read between the lines reads “More great news to be announced soon”

    The question is how soon is soon?

  6. Would the additional Phase 2 study be a duplicate of the Phase 2 that was just completed or would this be testing out a variation in dosing or formula?
    This last trial lasted a year so id hate for them to spend another year doing the exact same testing.
    But at least they are not abandoning it so thats a plus

  7. Phase 3 could no way commence in 2020, clearly it would be in 2021, all of ’21 trials, ’22 results etc, then filing…

    Sorry but Aclaris is 2023 earliest maybe even 2024

  8. @Admin … off-topic

    Histogen … what Actually is this? As per Histogen Pipeline Cosmetic CCM (Multipotent Cell Conditioned Media) has already launched

    http://www.histogeninc.com/technology/#development-pipeline

    When I read this correctly it should be very effective:

    http://www.histogeninc.com/applications/hair-stimulating-complex/

    “Two proof-of-concept clinical trials of an earlier prototype of CCM were completed outside the US, revealing promising efficacy results. In one trial, 84.6% of patients receiving just one treatment showed a significant increase in terminal hair count and hair thickness at 12 weeks. Improvement of hair growth parameters was still evident after one year.

    In the second clinical trial, in which patients received two treatments 6 weeks apart, the increase in total hair count was 46.5% above that seen after a single treatment. Significant improvements were observed in total hair count, terminal hairs and hair thickness at 12 weeks. At one year, hair growth parameters remain substantially above baseline.

    The two completed clinical trials have also revealed efficacy in traditionally difficult-to-treat hair loss populations. Subjects receiving treatment in the temporal recession, which is known to be more difficult to treat than other areas of hair loss, saw marked improvement in terminal hair count, with a mean increase of 22.6% at 12 weeks and 25.2% at the 24 week time point. In both trials, men over 40, normally less responsive to non-surgical treatments, responded well to treatment, including a mean increase of 39% in terminal hairs and 19.4% in total hair count in this age group in the current trial.

    In addition, excellent hair growth response in women as well as men was observed in a small Investigator-Initiated Trial (US IND 114184):

    These clinical investigations have consistently demonstrated the efficacy of using growth factors targeted to the treatment of hair loss.

    Following these initial studies, Histogen plans to conduct a Phase 1 Clinical Study in the US using HSC660, which is purified to enrich for KGF, VEGF, and follistatin and additional growth factors known to be necessary for hair growth: placental growth factor, angiogenin and hepatocyte growth factor.”

  9. Admin are they saying that stat5 inhibition could very well help people with Androgenic alopecia?

    If so any novel stat5 inhibitors?
    I think jak2 inhibits stat 5 activation

  10. An off topic question:

    For people that would like to lower their natural hairline, all these regrow treats won´t be from help.

    Which future treatment / method do you think will help with that or will a hairtransplant still be the only solution with that long lasting regrow process/healing/red head, a hair transplant brings with it.

  11. So I’m totally confused with Histogen. They are back at phase 1 now for HSC? I thought they completed two phases and are working phase 3 in mexico? Wtf is up with this company. Can someone please explain what this new phase 1 is about? New version of HSC and starting from scratch? Are they moving forward with phase 3 Mexico and this phase 1 is trial for USA fda?

    This is getting so freaking exhausting. Just release a new hair loss treatment already wtf! It’s just hair for goodness sake not the pill for eternal living.

    1. @Mjones I guess the Phase 1 will be a combination of HSC with some other shit …

      “Following these initial studies, Histogen plans to conduct a Phase 1 Clinical Study in the US using HSC660, which is purified to enrich for KGF, VEGF, and follistatin and additional growth factors known to be necessary for hair growth: placental growth factor, angiogenin and hepatocyte growth factor.”

      So this will not effect the Phase 2 and 3 for now. They Maybe just check if HSC will be boosted by other growth factors.

  12. I’ll say it once and I’ll say it again, cots will bring our next real effective treatment.

    Histogen just pissess me off. Just scrap the hsc trial. Never seen a company take so long to start a phase 1. I mean it ridiculous and f going to Mexico to get my head injected.

    I hope for riken, sisheido for the real deal cure but the time that gets approved by the fda it will be another 10 years.

      1. It sounds a lot easy than you make it sound Greg. Ideally you are absolutely right. However, for me, I like the treatment place to be where I live. If something goes wrong I can easily go back. I feel like it’s a huge hassle and mistakes can be made going back and forth. Maybe im just thinking silly. I do trust Japan. Hsc in Mexico most definitely not. Histogen should have completed all trials in the USA.

        1. @Mjones I most definitely agree. There are a lot of benefits to having a local clinic and the other stuff you mentioned. Plus, in 5-10 years when the FDA approves these treatments, cloning will probably be the least they can do. I too trust Japan – at least the bigger companies, but not Mexico.

          There’s a company in Mexico called “GIOSTAR” which offered me a stem cell treatment fo hair loss. BIG scam. Got it done at my local clinic. It’s better to wait a year or two after these kinds of procedures release to see how they perform over a wide range of people.

          I personally might get it done in Japan but waiting a little while is a wise move.

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