Aclaris lays off 46% of staff, resurrects zunsemetinib as potential cancer treatment

Aclaris Therapeutics has decided to give its MK2 inhibitor zunsemetinib a second chance—unfortunately, almost half of the biotech’s workforce won’t be so lucky.

The Pennsylvania-based company is reducing its headcount by around 46%, with the changes to begin “immediately” and likely to be completed by the end of June next year. The company entered 2023 with 100 full-time employees, all of whom were based in the U.S.

In a post-market release Dec. 19, CEO Douglas Manion, M.D., linked the decision to the reduction of zunsemetinib’s prospects after the drug failed to match placebo on any primary or secondary endpoints in a phase 2 rheumatoid arthritis trial last month.

“With the discontinuation of development of ATI-450 for immuno-inflammatory disease indications, we are taking steps to reduce our spending and streamline our organization, which we expect to meaningfully preserve capital,” Manion said.

When it first announced the zunsemetinib failure in November, Aclaris explained that it would halt all work on the MK2 inhibitor, also known as ATI-450, including a phase 2 trial in psoriatic arthritis. However, the biotech revealed in yesterday’s release that while the arthritis ambitions are gone for good, the company has decided to explore zunsemetinib as “a potential treatment for pancreatic cancer and metastatic breast cancer as well as in preventing bone loss in patients with metastatic breast cancer.”

Aclaris was originally pursuing these indications via its other MK2 inhibitor, dubbed ATI-2231, undergoing a phase 1 trial in collaboration with Washington University. However, the company said yesterday that “due to ATI-450’s more advanced clinical development package” the lead asset was a better fit.

In the meantime, the company will be holding out hope that better clinical news arrives when a 250-patient phase 2b trial of its topical JAK 1/3 inhibitor, called ATI-1777, reads out topline results in January.

“If the results of the phase 2b trial are positive, we intend to seek a commercialization partner for the asset,” Manion said.

It’s less clear what the future holds for ATI-2138. As recently as last month, Aclaris had been expecting to begin a phase 2 of the oral covalent ITK/JAK3 inhibitor in ulcerative colitis in “early 2024,” with further indications set to follow. Now, the company is apparently “reassessing the most effective pathway for ATI-2138 … including the indication selection due to the evolving competitive landscape within ulcerative colitis.”

Against a backdrop of Eli Lilly’s mirikizumab joining the increasingly crowded ulcerative colitis market, Aclaris plans to provide further guidance on its plans for the drug in early 2024.

November’s phase 2 fail wasn’t the first time that zunsemetinib disappointed in the clinic. Back in March, the drug failed to improve abscesses in patients with a chronic skin condition called hidradenitis suppurativa. Those mid-phase results halved the company’s stock to less than $6, with last month’s news taking the share price to new lows. The stock closed Tuesday trading at $1.02 per share.