Category Archives: Aclaris Therapeutics

Aclaris Therapeutics, AGA-201, ATI-502, JAK Inhibitors

Aclaris Announces Positive 6-Month Results for Androgenetic Alopecia

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Update: July 2020 — Unfortunately, Aclaris ceased work on JAK inhibitors and androgenetic alopecia in 2020. Moreover, new findings from July 2020 suggests that JAK inhibitors do not help AGA sufferers.

Update: Dr. Neal Walker interview.

Note: Some great photos are in their investor presentation from today. Pasting a couple below after getting permission.

Aclaris JAK Inhibitor Before After Male
Aclaris topical JAK inhibitor before and after photo in a great responder.

Aclaris Topical JAK Inhibitor Works for AGA

Huge news from Aclaris Therapeutics. They have just announced that their much anticipated topical Janus Kinase (JAK) inhibitor product (ATI-502) gave positive hair growth results in patients with androgenetic alopecia (AGA).

The results are for their interim 6-month Phase 2 open-label clinical trials of ATI-502 (also called AGA-201) in humans. 22 males and females participated in the trials till completion, including hair growth measurements. They applied ATI-502 to their scalp twice daily for 26 weeks.

Investigators rated 73% of subjects (16/22) as experiencing increased hair growth, and a higher 82% of subjects thought they saw increased hair growth through self-assessment.

Topical JAK Inhibitor Hair Growth
Modest hair growth after topical JAK inhibitor application for 6 months.

For a long time, many people did not believe that JAK inhibitors could result in hair growth in patients with androgenetic alopecia (i.e., male pattern hair loss). All the results in humans to date had only shown efficacy in patients with alopecia areata (AA), an inflammatory rather than hormonal condition.

Aclaris JAK Inhibitor Trials to Continue

I may add more to this post later, but for now the most significant quotes:

“The overall change was an increase of 8.6 hairs/cm2. Target area hair count increase was 15.3 hairs/cm2 in female subjects and 5.6 hairs/cm2 in male subjects.”

Per Aclaris CEO Dr. Neal Walker:

“This finding demonstrates that inhibiting a non-hormonal and inflammatory-mediated pathway may be an option for the treatment of AGA.”

“Through recent formulation work, Aclaris can achieve significantly higher topical concentrations of ATI-502.”

There was one “unrelated” case of breast cancer among the trial patients, but no-one else had any adverse side effects. I am sure everyone will look in detail at the side effect rates when 12-month trials are completed.

In the first half of 2020, Aclaris plans to initiate a double-blind, randomized, controlled Phase 2 dose-ranging clinical trial with higher concentrations of ATI-502. “With potentially, a female focus.” I hope that just means more females than males, and not just “only” females.

I do not think that this will be a cure for male and female pattern hair loss by any means. Perhaps a highly effective treatment in some patients. Moreover, for those of us who have major itching associated with our hair loss, perhaps we also have an inflammatory component to our hair loss as I have postulated in the past. Maybe the itchiest patients will see the best results?

Worth checking out ACRS stock price movement today.

Congratulations to the biggest JAK inhibitors for AGA fan of them all: blog reader “nasa_rs”.

Aclaris Therapeutics, Angela Christiano, Etienne Wang, JAK-STAT, TREM2

Aclaris Therapeutics and Mechanism of Action

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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.