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